Method for screening a patient for alzheimer&#39;s disease

ABSTRACT

The present system is directed in various embodiments to devices, systems and methods for detection, evaluation and/or monitoring olfactory dysfunction by measuring and determining the patient&#39;s olfactory detection threshold for the left and the right nostril. More specifically, the present invention relates to devices, systems and methods for detecting an asymmetric differential in a patient&#39;s olfactory detection threshold (left vs right nostril) which, when present, may be used as a tool to screen, detect, diagnose and/or monitor relative olfactory deterioration resulting from Alzheimer&#39;s disease. A preferred embodiment comprises cascading aromas by serially administering more than one pure odorant to the patient&#39;s nostrils, left vs right, with measurement of the time, or numbers of breaths, required to cognitively notice the pure odorants&#39; presence.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 14/795,606,entitled “Devices, Systems and Methods for Detecting a BilateralDifferential in Olfactory Detection Threshold for Pure Odorants”, andclaims priority to App. Ser. No. 62/023,352, entitled “Improved Devices,Systems & Methods For Quickly Detecting Bilateral Differentials InOlfactory Threshold, Presenting A Cascading Plurality Of Pure Aromas”,filed Jul. 11, 2014, and to App. Ser. No. 62/108,239, entitled “MethodFor Screening Bilateral Differentials In Olfactory Aroma Detection AndConfirming Alzheimer's Disease Through Retinal Plaque Deposits”, filedJan. 27, 2015, the entire contents of each of which are herebyincorporated by reference.

FIELD OF THE INVENTION

The present invention generally relates to devices, systems and methodsfor determining relative bilateral olfactory detection thresholds. Morespecifically, the present invention relates to devices, systems andmethods for detecting an asymmetrical differential in a patient'solfactory detection threshold as measured at the left and right nostrilsand that, when present, a significant asymmetrical differential mayindicate olfactory deterioration and may, therefore, be used as ascreening tool for Alzheimer's disease.

DESCRIPTION OF THE RELATED ART

Aroma testing in the past has been generally related to the overallaroma detection of a person, commonly by naming a particular odor,without particular interest in comparing the relative smelling abilityof their nostrils or the type of aromas they could and could not smell.Published articles document that a relatively poor sense of smell in theleft nostril, or sensitivity, as compared to the sensitivity of theright nostril may be indicative of early brain damage due toneurological disease. See, e.g., Murphy, et al., “Left hippocampalvolume loss in Alzheimer's disease is reflected in performance on odoridentification: A structural MRI Study”, Journal of the InternationalNeuropsychological Society, Vol. 9, No. 3, pp 459-471 (2003). This isthe case in Alzheimer's Disease (hereinafter AD), but is of clinicalsignificance in the early detection of AD, however, only if the aromaused in the test is a pure aroma for reasons that are discussed furtherinfra.

It is estimated that up to 40% of the elderly have undiagnosed earlyon-set Alzheimer's disease, but have not been diagnosed as theirdementia is quite mild at this point. Under these circumstances, anearly diagnostic tool, e.g., before clinically detectable dementia isobserved or diagnosed, is critical to enable therapies to be initiatedto slow, or perhaps even reverse, the progression of the disease.

Improved diagnostic screening methods useful in living people include:various blood tests, many seeking to identify specific lipids seen onlyin advanced AD patient's blood. Aroma detection screens, genetic marketsfor AD, radiological procedures, written cognitive tests on paper or oncomputer devices have all been improved with varying levels of efficacy.Amyloid Plaque deposit detection in eye tissue and other screeningmethods, seek to detect telltale precursors of AD before significantdamage is done to the brain.

Another screening methodology takes advantage of the notable deficit ofsmelling ability in the left nostril as compared to the smelling abilityof the right nostril to detect a pure aroma, appears according toprevious medical research, to be indicative of early neurologicaldegeneration of the olfactory nerve, specifically as seen in the earlyonset of AD.

The olfactory nerve is found on the left side of the brain and is notreversed bilaterally as many brain functions are, such as eye sight.Research, including data from autopsies, indicates that degeneration ofthe olfactory nerve occurs gradually and begins very early in thedisease development of AD. Such deterioration may begin years beforesubstantial dementia becomes notable. Thus currently a diagnosis of ADbecomes confirmed by existing testing procedures that are generallyfocused on observation, detection and/or diagnosis of actual dementia.This is problematic in the detection of AD because, inter alia, dementiapresents in other non-AD diseases, conditions and/or disorders.Moreover, at such late disease stages, AD is generally not amenable totreatment. Consequently, screening and diagnosis at the earliest stagepossible is critical.

The “pure odorant detection threshold” is the point at which anincreasing concentration of pure odorant molecules saturate theolfactory nerve to the extent that a cognitive reaction first takesplace, where the patient recognizes they are smelling something, buthaven't yet cognitively been able to identify the odor by name. There isa latent period between introduction of the pure odorant molecules intothe patient's nostrils and when the pure odorant detection threshold isreached. Measurement of this latent period can be of clinical utility.In the case of early onset AD, the latency in the left nostril may begreater than that of the right nostril, providing very early clinicalindication of the presence of AD. The olfactory function differentialfavoring the right side disappears in well advanced AD, as the entirebrain deteriorates the right side catches up in deterioration so thatboth sides are profoundly impacted.

The “pure odorant identification threshold” represents a slightly longerlatent period than the “pure odorant detection threshold” as it is thepoint at which the patient is able to cognitively process the odor andthen actually identify the odorant by name.

A general process for measuring the left nostril latent period andrelated bilaterally asymmetrical olfactory nerve deterioration isrecently described in the “peanut butter aroma test” reported byJennifer Stamps at the University of Florida. The Stamps method uses asimple but effective protocol where a common centimeter ruler is held upto the nose of the test subject. The subject is instructed to closetheir eyes and cover one nostril as a spoonful of peanut butter, a pureodorant as defined infra, is slowly moved towards their nose. Theclinical technician notes the estimated distance in centimeters betweenthe aroma source and the nostril of the test subject at the point thefirst aroma detection threshold is noted by the subject. Two testingevents might result in the following exemplary pure odorant olfactorythreshold values: 12 centimeters on the left nostril and 21 centimeterson the right nostril.

Both the left and right nostrils were tested several times under theStamps methodology and in random order with a 90-second “reset period”between trials to clear the olfactory gland of the odorant. The relativesmelling ability of the two nostrils were then compared using knownstatistical techniques. Effectively, the Stamps method amounts to anindirect measurement of concentration required for cognitive notice ofpeanut butter aroma presented to a nostril, based upon reducing thedistance between the aroma source and the nostril. Stamps uses a singlepure odorant with an endpoint identified as the distance from aromasource to the nostril at the transition point where no scent is detectedto a scent cognitively noticed. Stamps, therefore, uses the “pureodorant identification threshold” as an endpoint.

“Pure odorant”, also referred to equivalently as “pure aroma” or “aroma”herein, is defined as substances including molecules and/or compoundswhich principally stimulate the olfactory cell receptors associated withthe first cranial nerve and that do not trigger or excite the trigeminalnerve associated with the fifth cranial nerve.

Thus, the use of a “pure odorant” for aroma testing is critical in thecontext of, inter alia, detection of relative deterioration of smellingsensitivity in the left nostril compared with the right nostril.

However, the Stamps method presents some obvious issues rendering itgenerally unacceptable for repeatable and robust clinical results.Namely, Stamps fails to consider patients' nasal structural issues whichmay contribute to low airflow and may contribute to poor thresholddetection ability in a given nostril. In addition, Stamps fails toconsider the general airflow within the testing environment and how thatmay impact the test results. It is clear that commercialization of themethodology requires a well-defined clinical protocol and more accurateand robust devices and testing methods. Stamps also requires an at least90 second reset period between screening events to allow the subject toprepare for the next aroma presentation. This “reset” period wastesvaluable time and variations from person-to-person may require longerthan the prescribed 90 second period. Stamps also fails to use the “pureodorant detection threshold”, opting instead for the later-in-time “pureodorant identification threshold”. Finally, Stamps fails to recognizethe advantage of “olfactory sensory dissonance” defined as a phenomenonwhereby an aroma having been noticed by a subject, that declines inperceptive concentration as it is replaced by an increasingconcentration of a second aroma tends to crisply shift full cognitivenotice to the second aroma and the first aroma is then quicklyforgotten.

Nonetheless, the Stamps test and other related previously publishedresearch papers support the conclusion that an inability to detect asingle pure aroma or odorant relatively equally in both nostrils,especially when the deficit is more notable in the left nostril, mayindicate olfactory nerve damage and, therefore, indirectly the earlyonset of AD.

Applicant has developed several solutions to the problem of bilateralscreening as further described in U.S. patent application Ser. No.14/282,622, entitled DEVICES, SYSTEMS AND METHODS FOR DETECTING ABILATERAL DIFFERENTIAL IN OLFACTORY THRESHOLD FOR PURE ODORANTS, theentire contents of which are hereby incorporated by reference.

A chain of scientifically based facts are behind aroma detectionscreening to detect damage to the olfactory nerve, also referred to asthe first cranial nerve:

1. There are a number of “pure odorants” that can only be detected bythe olfactory nerve and not the trigeminal system.

2. Autopsy results indicate that the earliest indications of AD occurnear the olfactory nerve on the left side of the brain.

3. The olfactory nerve is anatomically located behind the left nostril.

4. The loss of the sense of smell for pure aromas occurs first on theleft side of the brain proximate the olfactory nerve in the ADdevelopment process.

5. The right nostril can act as a control to find a relative strength ofthe nostrils as a ratio.

6. An increasing concentration of pure aroma triggers a cognitive noticemost people are aware of and can cognitively react to.

7. Due to the phenomenon of olfactory sensory dissonance an aroma havingbeen noticed by a subject, that declines in apparent concentration as itis replaced by an increasing concentration of a second aroma that tendsto crisply shift full cognitive notice to the second aroma and the firstaroma is then quickly forgotten.

Bilateral aroma testing may, but need not, include comparison using aknown absolute concentration of aroma for scientific validation.Instead, a preferred embodiment may comprise a relative comparison, infinding which nostril is sensitivity is greater or weaker. Somevariation is normal, but a profound difference is likely significantbaring identifiable medical reasons for the loss of symmetricalsensitivity.

Thus, the “relative sensitivity” of the two nostrils is a preferredvariable being sought for olfactory damage assessment, rather than“absolute sensitivity” using embodiments of the present invention.

Some people have been exposed to industrial chemicals or paints thathave damaged their sense of smell. However such chemicals likelyimpacted both nostrils relatively equally since such damaging chemicalexposure was equal. In addition, research indicates that a relativeequal loss of the sense of smell for pure aromas on both sides, ascompared to a normal detection level, might be indicative of otherneurological diseases, such as Parkinson's disease which impacts bothnostrils equally.

Surgery or a serious brain infection or serious head trauma for example,might render one nostril's sensitivity damaged or completely unable tofunction without presenting an accurate indication of AD linkedolfactory damage. Some people are genetically handicapped in their senseof smell for pure aromas lacking any known trauma.

A deviated septum might reduce air flow on the affected side which mightskew results slightly in favor of the non-impacted nostril. Actual fieldtesting data indicate that the effect of a restricted airway is not asmuch an issue as anticipated, but the condition still needs to beconsidered. Congestion and other reasons for temporary odor sensitivityimpaction need to be eliminated or considered as a disqualification forthe aroma screen in severe cases. An alternative AD screen should thenbe used, such as the cur cumin retinal study.

Generally however, according to studies, a deteriorated sense of purearoma or odorant detection in the left nostril is neurologicallysignificant when the subject is screened. Such pure aroma screensindirectly assess the condition of the olfactory nerve by presentingpure aroma in a controlled way, such that the concentration and sort ofaroma is manipulated by the testing personnel and only one nostril at atime is served aroma. The relative strength of the nostrils is themetric of interest in detecting AD.

All known early onset AD screening methods lack a uniform staging systemfor measuring and communicating the relative state of a patient's ADdevelopment. A uniform disease risk staging system needs to beestablished similar to the cancer staging of 1-4. Various cancers havewell defined staging methods. Different cancers have different criteriafor staging wherein stage 1 is less serious than stage 3, for example.

A common diagnostic scoring metric for AD would advance medical researchstudies by, inter alia, universally defining AD developmental stages.

Further, a risk factor scoring method that takes the totality of apatient's medical history and the various AD screening methods intoaccount to render an AD “risk factor” is also badly needed. These twometrics would sort people into those with a low risk factor, a high riskfactor without AD and an actual AD stage.

A staging metric would also help Doctors diagnose AD earlier and with agreater level of confidence than has been previously possible withliving patients. AD diagnosis at an earlier point in disease developmentwill benefit the patient by facilitating more efficacious early ADtreatment, hopefully before significant brain damage occurs.

An AD scaling method would also provide a pool of qualified candidatesat various stages of the disease for clinical trials of potentiallyefficacious drugs. Having access to a large pool of known early onset ADpatients would certainly advance clinical studies dramatically.

However, all known AD screening methods have various unrelatedAlzheimer's Disease risk scoring systems, or none at all. Therefore,these screens fail to offer doctors an overall AD risk factor in thecontext of the full medical history for that particular patient. Ameaningful and fundamentally helpful report for Doctors to use indeciphering and communicating the actual risk of a certain patientdeveloping AD in the future is sorely needed.

An efficacious AD risk factor report for doctors enables the renderingof a firm diagnosis of Alzheimer's disease based upon a clear medicalstandard that can be universally understood and communicated. Typically,AD cases are not firmly diagnosed until all alternative causes ofdementia that is clearly presented, have all been ruled out.

An Alzheimer's disease risk factor scoring system that is able toencompass all the various relevant medical history issues as well asinterpret efficacious AD screens, that have been performed on theliving, is needed to provide medical practitioners diagnosticinformation in a useable form. The staging method needs to look at theoverall data for a particular patient to put all the data into a propercontext. An accepted system for staging Alzheimer's disease is currentlylacking due to the previous difficulty in even confirming that aparticular patient actually has the disease at all, prior to theautopsy.

Amyloid plaque deposits and protein tangles are the microscopic evidencesought to confirm AD in diseased patients in autopsy. Amyloid plaquedeposits also appear in the retina and iris and are visible with variousstains that jump the blood brain barrier and are fluoresced by specificspectrums of light. Thus, is possible to observe plaque deposits in theeye of a living person non-invasively and deduce from what is seen inthe eye what would be apparent if the brain cavity were opened.

A patient suffering some dementia (which easily diagnosed with cognitivetesting), who has a notable deterioration of sensitivity to pure aromaon the left side, without a known medical reason, who also has had abaseline retinal photograph examined by an ophthalmologist and then hada cur cumin plaque detection study done which identified amyloid plaqueon their retina, almost certain has AD. The relative amount of amyloidplaque seen is directly proportional to the stage of AD.

Other neurologic screening methods, e.g., the University ofPennsylvania's “UPSIT” aroma sensitivity screen claim to identifyolfactory and scent memory problems, but fails to differentiate betweenthe two nostrils, and therefore fails to identify any odorant thresholddifferential between the nostrils. Further, the UPSIT scratch and sniffscent identification test fails by design to differentiate between purearomas that are perceived exclusively by the olfactory organ or harshersmell by the trigeminal system. Mixing Lemon and Gasoline in one test iscertainly behind the times in olfactory research.

In our research we discovered that the fidelity of the scratch and sniffsamples is amazingly poor. The ink used for scratch and sniff printingrequires that odorants used be completely free of water, which requireschemical approximations of scents rather than actual essential oils orthe like. The UPSIT also uses combinations of aromas that certainly arenot universally familiar to people. Bubble Gum for example comes in manyflavors which makes it tricky to pick the aroma the testers expected.

In a small clinical trial performed by Inspired Technology the scratchand sniff scent for Orange was thought to be Bubble Gum by 7participants, Cheddar Cheese by 1 with 2 not hazarding a guess with noone of the 10 recognizing Orange. Cheddar Cheese on the other hand wasthought by 8 out of 10 to be paint thinner with no one guessing CheddarCheese. Lemon was thought to be Motor Oil by 7 out of 10 participantswith one hazarding Rose.

The UPSIT is also culturally biased as familiar scents in the USA arenot so familiar in India, for example. Thus, a test media that usesactual essential oils, with a device that differentiates the nostrilsand has a way to offer a plurality of aroma test sets at little expense.

Consequently, the UPSIT data cannot be used as an accurate screeningmechanism for at least AD.

Thus, a need exists in the art generally for an inexpensive, easy touse, accurate and repeatable clinically significant device, system andmethod for detecting an asymmetric (left vs right) differential in theolfactory detection threshold of a patient, preferably without arequired “reset” period. Such devices, systems and methods may be usedto assist a physician in screening and/or detecting AD and/or risk ofdeveloping AD, before the clinical presentation of dementia occurs.

The present invention addresses these, among other, needs.

BRIEF SUMMARY OF THE INVENTION

The present system is directed in various embodiments to devices,systems and methods for detection, evaluation and/or monitoringolfactory dysfunction by measuring and determining the patient'solfactory detection threshold for the left and the right nostril. Morespecifically, the present invention relates to devices, systems andmethods for detecting an asymmetric differential in a patient'solfactory detection threshold (left vs right nostril) which, whenpresent, may be used as a tool to screen, detect, diagnose and/ormonitor relative olfactory deterioration resulting from Alzheimer'sdisease. A preferred embodiment comprises cascading aromas by seriallyadministering more than one pure odorant to the patient's nostrils, leftvs right, with measurement of the time, or numbers of breaths, requiredto cognitively notice the pure odorants' presence and without a reset orclearing period between presentation of successive odorants. The devicedisclosed is also useful for scent identification tests and scentconcentration tests as a testing platform.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a cross-sectional front view of one embodiment of thepresent invention.

FIG. 2 illustrates a cross-sectional front view of the embodiment ofFIG. 1 in exhalation mode.

FIG. 3 illustrates a cross-sectional front view of the embodiments ofFIGS. 1 and 2 in inhalation mode.

FIG. 4 illustrates a top view of one embodiment of a flap valve.

FIGS. 5A and 5B illustrate a top view of two embodiments of amulti-chamber odorant or pure odorant cartridge.

FIG. 6A illustrates a ratcheted gear advancer mechanism.

FIG. 6B illustrates a wound spring gear advancer mechanism.

FIG. 7A illustrates one embodiment of a valve member sheet.

FIG. 7B illustrates one embodiment of an individual valve member.

FIG. 8A illustrates a perspective and exploded view of a glass jar withthreaded cap.

FIG. 8B illustrates a cross-sectional front view of one embodimentcorresponding to FIG. 8A.

FIG. 8C illustrates an exploded view of the embodiment of FIGS. 8A and8B.

FIG. 9A illustrates a perspective and partial exploded view of oneembodiment of the present invention.

FIG. 9B illustrates a perspective exploded partial view of theembodiment of FIG. 9A.

FIG. 9C illustrates a partial cutaway front view of the embodiment ofFIGS. 9A and 9B.

FIG. 10A illustrates a front view of one embodiment of the presentinvention with active left nostril odorant or pure odorant pathing.

FIG. 10B illustrates a front view of one embodiment of the presentinvention with active right nostril odorant or pure odorant pathing.

FIG. 11A illustrates a front view of one embodiment of a loaded pureodorant or pure odorant cartridge.

FIG. 11B illustrates a side view of the embodiment of FIG. 11Aillustrating the loading of an odorant or pure odorant into thecartridge.

FIG. 11C illustrates a perspective view of one embodiment of the presentinvention.

FIG. 12A illustrates a side exploded view of one embodiment of anodorant or pure odorant cartridge.

FIG. 12B illustrates an exploded view of one embodiment of odorant orpure odorant cartridge.

FIG. 12C illustrates a side cutaway view of one embodiment of odorant orpure odorant cartridge.

FIG. 12D illustrates a side cutaway view of one embodiment of odorant orpure odorant cartridge.

FIG. 12E illustrates a side cutaway view of one embodiment of odorant orpure odorant cartridge.

FIG. 12F illustrates a side view of one embodiment of odorant or pureodorant cartridge.

FIG. 13A illustrates a side and cross-sectional view of one embodimentof the present invention in active nostril inhalation mode.

FIG. 13B illustrates the embodiment of FIG. 13A in active nostrilexhalation mode.

FIG. 13C illustrates the embodiment of FIGS. 13A and 13B in passivenostril inhalation and exhalation mode.

FIG. 14A illustrates a top view of one embodiment of odorant or pureodorant cartridge.

FIG. 14B illustrates a top view of a layer of material for oneembodiment of the odorant or pure odorant cartridge.

FIG. 14C illustrates a side cutaway view of one embodiment of thepresent invention.

FIG. 15A illustrates a top cutaway view of one embodiment of the presentinvention.

FIG. 15B illustrates a top cutaway view of one embodiment of the presentinvention.

FIG. 16A illustrates a side view of one embodiment of the presentinvention.

FIG. 16B illustrates a front view of one embodiment of the presentinvention.

DETAILED DESCRIPTION

While the invention is amenable to various modifications and alternativeforms, specifics thereof are shown by way of example in the drawings anddescribed in detail herein. It should be understood, however, that theintention is not to limit the invention to the particular embodimentsdescribed. On the contrary, the intention is to cover all modifications,equivalents, and alternatives falling within the spirit and scope of theinvention.

The present system is directed in various embodiments to devices,systems and methods for detection, evaluation and/or monitoringolfactory dysfunction by measuring and determining the patient'solfactory detection threshold for the left and the right nostril. Morespecifically, the present invention relates to devices, systems andmethods for detecting an asymmetric differential in a patient's relativeolfactory detection threshold (left vs right nostril) which, whenpresent, may be used as a device to detect, diagnose and/or monitorolfactory deterioration resulting from Alzheimer's disease.

DEFINITIONS

As used herein, “symmetric” or “symmetrical” means that there is not asignificant differential in the subject patient's ability to detectand/or identify odors between odors administered and/or inhaled into thepatient's left nostril vs. the patient's right nostril as measured bythe olfactory threshold determined for each nostril.

As used herein, “asymmetric” or “asymmetrical” means that there is asignificant asymmetry or differential in the subject patient's abilityto detect and/or identify odors between odors administered and/orinhaled into the patient's left nostril vs. the patient's right nostrilas measured by the olfactory threshold determined for each nostril.

“Hyperosmia” is defined as increased olfactory acuity, or a decreasedthreshold for detecting odors, and may be symmetric or asymmetric asthose terms are defined herein. Various embodiments of the presentinvention may detect and/or monitor hyperosmia or treatments therefore.

“Hypoosmia is defined as diminished or decreased olfactory acuity, or anincreased threshold for detecting odors, and may be symmetric orasymmetric as those terms are defined herein. Various embodiments of thepresent invention may detect and/or monitor hypoosmia or treatmentstherefore.

“Anosmia” is defined as the inability to recognize odors and may besymmetric or asymmetric as those terms are defined herein. Variousembodiments of the present invention may detect and/or monitor anosmiaor treatments therefore.

“Dysosmia” is defined as the abnormal sense of smell and may besymmetric or asymmetric as those terms are defined herein. Variousembodiments of the present invention may detect and/or monitor dysosmiaor treatments therefore.

“Olfactory dysfunction” is defined herein as a patient with a disorderand/or condition with one or more of the following: hyperosmia,hypoosmia, anosmia, and dysosmia. The olfactory dysfunction may besymmetric or asymmetric as those terms are defined herein.

“Pure odorant”, also referred to equivalently as “pure aroma” is definedas substances including molecules and/or compounds which principallystimulate the olfactory cell receptors associated with the olfactorynerve, aka the first cranial nerve, and that do not trigger or excitethe trigeminal nerve associated with the fifth cranial nerve. Anon-exhaustive and categorized listing of pure odorants follows:

The pure odorant Spice family comprises:

Cinnamon;

Clove;

Vanilla;

Nutmeg; and

Allspice.

The pure odorant Food family comprises:

Peanut/Peanut Butter;

Coffee;

Cocoa;

Apple;

Almond (bitter); and

Strawberry.

The pure odorant Herbal family comprises:

Peppermint;

Spearmint;

Wintergreen;

Allspice;

Parsley;

Sage;

Turmeric;

Thyme;

Basil;

Dill weed;

Caraway;

Anise;

Fennel;

Mace;

Palmarosa; and

Patchouli.

The pure odorant Floral family comprises:

Rose;

Lemongrass;

Rosemary;

Lavender;

Lilac;

Violet; and

Origanum.

The pure odorant Citrus family comprises:

Orange;

Tangerine;

Lemon;

Lime;

Mandarin;

Grapefruit;

Bergamot and

Petitgrain.

The pure odorant Wood and Resin based family comprises:

Eucalyptus;

Juniper berry;

Pine;

Tea tree;

Spruce;

Ho wood;

Cypress;

Cedar;

Birch;

Fir;

Cajeput;

Camphor;

Cassia;

Citronella;

Clary;

Copaiba;

Elemi;

Hydacheim;

Litsea; and

Niaouli.

“Pure odorant detection threshold” is defined as the point at which theconcentration of pure odorant molecules saturate the olfactory nerve tothe extent that a cognitive reaction first takes place. At this point,the subject patient is able to express that he or she is smellingsomething, but not necessarily able yet to identify the aroma by name.The pure odorant detection threshold may be found to be asymmetrical,i.e., significantly different as between the nostrils, indicatingolfactory dysfunction. Alternatively, the pure odorant detectionthreshold may be found to be symmetrical between the tested nostrils.

“Pure odorant identification threshold” represents a slightly longerlatent period than the “pure odorant detection threshold” as it isdefined as the point at which the patient is able to actually identifythe pure odorant by name, indicating that cognitive processing hasoccurred.

“Odorant” is defined herein as a compound that does trigger thetrigeminal nerve.

“Odorant detection threshold” is defined as the point at which theconcentration of odorant molecules saturate the olfactory nerve to theextent that a cognitive reaction first takes place. At this point, thesubject patient is able to express that he or she is smelling something,without necessarily identifying the aroma. The odorant detectionthreshold may be found to be asymmetrical, i.e., significantly differentas between the nostrils, indicating olfactory dysfunction.Alternatively, the odorant detection threshold may be found to besymmetrical between the tested nostrils.

“Odorant identification threshold” is defined herein as the point atwhich the patient is able to actually identify the odorant by name,indicating that cognitive processing has occurred. The odorantidentification threshold may or may not be symmetrical between thenostrils.

“Effective amount” of the odorant or pure odorant is defined as theamount of pure odorant required to infuse the aroma airway passageduring operation of the various devices, systems and methods of thepresent invention sufficiently to enable a patient to smell the pureodorant, i.e., when saturation of the olfactory nerve is sufficient toenable the reaching of the pure odorant detection threshold for thepatient and nostril being tested.

“Clear air”, also referred to as pure air, is defined as air that doesnot comprise the odorant used in the inventive embodiments of thepresent invention. Preferably, clear air comprises air that issubstantially uncontaminated by any odorant, including pure odorants.Clear air may comprise ambient air, i.e., atmospheric air, eitherfiltered or unfiltered, or air that is provided from a clear air sourcesuch as an air tank or nebulizer and/or from a mechanized powered airpump as is well known in the art.

“Reset Period” is defined as a rest time between presentations orintroductions of odorants or pure odorants, known reset periods are inthe range of 90 seconds.

Aroma detection testing is done for many reasons and in a number of waysto accomplish various purposes, including diagnostic medical tests. Odoridentification for example, comprises a common olfactory function thatis tested. Numerous odor identification devices and methods have beendeveloped to screen for what might be called a “scent memory function”.This sort of testing metric might be called “Tell me what you smell?”This corresponds to the presently defined “pure odorant identificationthreshold”. This endpoint for testing has several serious problems, notthe least of which is the required inclusion of cognitive identificationof the aroma or odor presented.

Pure aroma olfactory detection threshold response time is of particularclinical interest, especially when done bilaterally. In other words, thesame aroma sensing test is preformed separately on each nostril and thetest results compared, left nostril vs right nostril. This is donewithout aroma identification even being required. Perhaps the metriccould be called, “Tell me when you smell something.”

A Baseline of Pure Air Vs Aroma Laden Air as a Testing Metric

Concentrations of a single aroma may be gradually increased in unscentedair until cognitive awareness of the presence of the aroma is noted. Thedistance between the aroma source (a spoonful of peanut butter) and thenostril may be measured as a diagnostic metric upon the patient firstnoting the peanut butter aroma. “With your eyes closed and one nostrilcovered, tell me when you first smell the aroma, which I am slowlymoving closer to your nose along the ruler”.

Alternatively, the time interval can be measured in seconds betweenaroma presentation to the subject, who is inhaling through an aromapresentation device, until the time interval ends upon cognitive noticethat an aroma was noted. “Tell me the second you smell the aroma”. Timein seconds is the metric recorded, indirectly measuring the level ofodor concentration of aroma required to trigger cognitive notice.

Similarly, the number of breaths taken from the point of firstintroduction or presentation of the aroma until cognitive notice by thesubject is a valid metric indirectly scaling the aroma detection abilityof the nostrils.

The aroma presentation device might emit an audible tone when theexhalation portion of the breathing cycle is taking place to help thetesting personnel note the precise number of breaths taken during thepresentation of the aromas, in this mode of testing. The number ofbreaths taken before cognitive notice of the aroma is also an indirectmeasurement of the concentration of aroma required to get cognitivenotice, which measures olfactory function.

Finally, the metric of the absolute concentration of an increasing aromalevel required for cognitive notice, (as measured by an electronic nosemodule with a digital readout), may be used in the pure air vs aroma airladen air model of bilateral olfactory testing. A plurality of sample ofone pure aroma with a spectrum of dilutions might be presented with thesmallest concentration detectable ramped up in small steps to a strongerconcentration might be used with first one nostril and then the other todetect the weaker nostril.

The metric of single aroma might be considered comparing no smell in theair as a baseline compared to a slowly increasing concentration of purearoma infused in clear room and recording some definable metric used forclinical comparison between the nostrils. All of these metricsindirectly score olfactory function for detection of pure aromas.

Controlling the presentation of aroma may be done in a number of ways,each with advantages and disadvantages which may be mitigated withproper protocols and advanced device design.

1. Testing bilateral olfactory acuity using a contained and controlledaroma source has the advantage of removing the skewing effect of themovement of room air. A variable control completely lacking in thedistance to the nose method mentioned above. The aroma is introduceddirectly into the nostril of the person being tested with this method.

The aroma concentration is thus more consistent, controllable and theresults more repeatable when the aroma is contained and directed into anostril. Containing the aroma source and directing it into the nostrilof the test subject allows a precisely measured presentation of aromacontaining air, with the cognitive threshold sensitivity scored orquantified numerically in a number of ways. A reset period betweentesting events must also be allowed using any method that presents onlyone aroma since the comparison is no aroma vs aroma detected.

Containing aroma within a device presents potential issues with“mechanical latency”. Aroma molecules tend to stick to certain materialsmore than on others. Any amount of latent aroma tends to confuse thesubject of the screening, but it is possible to contain aroma withoutcontaminating the device and render the screen inaccurate, as will beexplained below.

2. The time in seconds between control air with no aroma present and acontrolled increasing concentration of aroma becoming detectable is auseful metric for bilateral aroma sensitivity testing. When the test isdone sequentially for both nostrils using the same device and same aromasource, the ratio of aroma sensitivity may be accurately tested by usingtime. The nostril that takes longer or requires a higher level of aromato recognize the presence of the aroma is the weaker nostril. A resetperiod between screening events is still required if only one aroma isused.

3. The number of breaths it takes to recognize the presence of an aromabeing presented beginning with breathing controlled air with no aromapresent is a potentially useful testing metric that has the advantage ofnot even requiring a clock. A reset period between screening events isrequired since only one aroma is being used.

4. Cascading a series of pure aromas presented to a single nostril wherethe number of seconds or the number of breaths required to cognitivelyrealize that an alternative pure aroma is presented generates meaningfuldata and can quantitatively rate the relative performance of the twonostrils. Using at least two pure odorants presented one after anothermakes a reset period between events unnecessary, which will save timeadministering the screen using this method.

Of all methods of aroma screening noted, the lack of a reset period isparticularly significant. When a plurality of aromas are presentedsequentially, the olfactory nerve and brain can only concentrate on onearoma at a time due to the phenomena of “olfactory nerve dissonance”.The function works to avoid our senses overwhelming us. We can ignorewhat we have sensed previously to be quickly ready to focus on somethingnew . . . and in prehistoric times, potentially dangerous.

It is a known phenomenon of the olfactory nerve that the human sense ofsmell is elegantly sequential in its ability to note a specific new odorand “forget” or ignore the previous aroma. This effect is called odordissonance. This feature of olfactory function is of significant utilityin bilateral pure aroma testing using a cascading method. This testmight be described as “tell me when the aroma you smell has changed to anew aroma” not “tell when you can smell one aroma” or “can you name thearoma”?

When an aroma is presented and a second aroma becomes notable, the brain“forgets” the previous aroma and concentrates on the fresh aroma.Cascading aromas thus takes advantage of that primitive neurologicaleffect to evade the reset period required in single aroma screeningmethods.

7. Odor identification tests generally contain a plurality of familiararomas which may be cognitively challenging to demented patients whostruggle to find the word in their failing memory that describes anaroma that seems familiar to them, but is hard to place its name. Simplyasking someone to note when the present aroma changes to a fresh aroma,as in the cascading screen, without being required to name the aroma isless taxing cognitively.

Most participants using a screen for AD will be older and likely alreadypresenting some dementia. While potentially helpful in confirminggeneral dementia, odor identification tests, especially unilaterally andwithout the distinction of the aromas being pure are worthless indiagnosing AD. Odor identification per se, simply has not proven to behelpful in detecting AD.

Thus, at least two pure odorants, or a plurality thereof, may becascaded without requiring the subject to identify any of the aromas andthe screen will still generate valid results. Should a subjectspontaneously name a pure odorant, no harm is done, but it is notrequired that the aroma be named or is it helpful to obtain validresults.

Cascading Aromas, an preferred alternative aroma detection screeningmetric;

Cascading a sequence of a plurality of pure aromas without a pure airreset period between aromas also scales the relative olfactorythresholds of the nostrils and has distinct advantages. The aromas maybe presented manually where the aroma device is advanced to present afresh aroma as the previous aroma is consumed or the device may bemechanically spring loaded, where the aromas are changed at the push ofa button by the test subject during the screen. Alternatively, more thanone device may be used to present the more than two odorants, or pureodorants to the patient.

The olfactory function of dissonance is far faster than “resetting” witha time delay, such as is required to reach a “no aroma detectioncondition” using clear air in preparation for a next aroma test event.The human olfactory latency period between having sensed a first aromaand being able to switch to sense a second aroma is far faster thangoing from aroma laden air to clear air.

The ability to ignore a first aroma and fully concentrate on a secondaroma is of significant utility in using a cascading pure aromathreshold testing method. This method uses a metric of “rapid sequentialaroma scoring”. “Cascading” a plurality of pure aromas, presented oneimmediately after another, ignores the currently required 90 secondreset period between aroma presentations. This method speeds up theoverall bilateral aroma testing process dramatically, as well asreducing scent latency issues.

The period of time, we shall call the “olfactory threshold latencyperiod” is an indirect measurement of the condition of the olfactorynerve, which is of clinical significance in detecting localizeddeterioration of the brain. Adding a number of such latency periodstogether creates a larger sample from which to more finely deduce therelative sensitivity of the nostril. Enlarging the aroma presentationdevice from 1 liter to 1.5 liters will increase the number of breaths orthe number of seconds it takes to note a fresh aroma. While the meannumber of breaths with a 1 liter aroma device appears to be 4, 50% morevolume will increase to 6 the average number of breaths per event.

Aroma presentation devices without an aroma chamber, such as the onepresented in FIG. 10 and higher, reduce the time spent breathing aromainfused air and allow an interesting plurality of aromas to fade in andout quickly.

The longer the latency period of one nostril, the weaker the sense ofsmell in that nostril. What we seek to detect is a significant relativedeficit, particularly on the left side rather than an absolute value.

Theoretically, and according to previous clinical testing, the longerthe period of time between exposure to aroma infused air and cognitivenotice of that aroma, the worse the olfactory deterioration is in aparticular nostril. The more time that is required to note the aroma, ora higher concentration of aroma required to trigger cognitive notice ofthat aroma, when tested bilaterally indicates relative olfactorydeterioration of the two sides. More breaths equal more time andrelative olfactory deterioration of the nerves associated with onenostril.

The memory function of an aroma, once cognitively recognized, (notnecessarily named) remains in the olfactory “queue” until replaced by asubsequent aroma. It is thus, very hard to concentrate on smelling morethan one aroma at a time. The new aroma replaces the previous aroma inour active olfactory memory.

“Olfactory aroma memory latency”, presents potential issues using asingle aroma vs the clear air (air with no detectable aroma) mode oftesting. It is hard to forget the recently presented aroma when onlycompared with theoretically clear unscented room air, making ushypersensitive to any latency of the first aroma. Unscented air in thatmethod of testing must be used to purge the olfactory nerve and thearoma presentation device of latent aroma in preparation for the nexttesting event. Olfactory aroma latency is defeated by cascading aplurality of at least two pure odorants without a reset period.

A “reset” of the olfactory nerve may be defeated by even the slightesthint of the recently presented aroma. Aroma which is still lingering inthe air or clinging to the airways of the aroma presentation device orthe nostril can easily contaminate otherwise clear room air and spoilthe sensitivity of the test. This is really the downfall of a one aromascreen.

While the recently presented aroma may be very faint after a resetperiod, the human sense of smell in some people is amazingly strong. Thearoma latency issue thus creates a potential problem in obtainingaccurate bilateral olfactory threshold sensitivity data with a clear airbaseline sort of test.

Faint mechanical latency and human aroma memory latency issues, whenusing a handheld aroma presentation device, may be successfully overcomeby “cascading” a new pure aroma immediately after another without usinga clear air “palate cleansing” interval between aroma testing events. Assoon as a first aroma is detected a subsequent aroma is stronglypresented causing the first aroma to fade from memory without theproblematic and time consuming step of clearing the olfactory “palate”with clear air.

A metric for bilateral olfactory threshold cascading testing isprovided:

The testing method and scoring metric of finding the sum of at least twoolfactory threshold detection periods, corresponding to at least twopure odorants, in seconds or in the number of breaths, derived frompresenting a series of pure aromas, presented sequentially one afteranother. The aromas are presented in rapid order to one nostril, withoutclearing the olfactory nerve with unscented air between pure the aromas.While using as few as 2 aromas may provide meaningful clinical data,since there are so many pure aromas to choose from a plurality of even20 such aromas develops a more interesting test and extends the testcycle which also presents more defined nostril sensitivitydifferentials.

The identical test is then run on the other nostril and cumulativeresults compared to scale the bilateral pure air aroma detectionthresholds of the patient. When the test subject notes that a new aromais sensed, the device is immediately advanced to the next aroma eithermanually or automatically with a spring loaded, indexed sort ofmechanical arrangement. A circular presentation method where the firstaroma is also the first and last sample presented has clinical merit.

A method for cascading aromas for aroma presentation devices with anaroma chamber.

A first aroma is presented and the test subject told to take threebreaths, upon the third exhalation, the device is advanced and thesecond aroma is immediately presented.

When the second aroma is sensed, a third aroma (if used) is immediatelypresented etc. This is done without a “reset period” using unscented airbetween the pure aromas presented.

A Method for Cascading Aromas

A first aroma is presented and the test subject told to take threebreaths, upon the fifth exhalation, the device is advanced and thesecond aroma is immediately presented.

When the second aroma is sensed, a third aroma (if used) is immediatelypresented etc. . . . This is done without a “reset period” usingunscented air between the pure aromas presented.

A few as two pure odorants may be used by cycling between them.Alternately, a large plurality of different pure aromas may be used.When the plurality of aromas have all been presented and the device hascycled back to the first aroma, the cumulative time elapsed clock isstopped and the seconds for that nostril recorded or the number ofbreaths taken is noted. Thus, the time in seconds between start and stoptones becomes the metric to be recorded for that nostril. Alternately,the sum of number of breaths per aroma is added up to scale the nostrilbeing tested.

An audible tone may also be emitted during the exhalation portion of thebreath cycle so testing personal can be aware of the number of breathstaken during the testing process and be aware of potentialhyperventilation and the number of breaths taken between tones is also ametric that may be of some utility.

The patient may be asked to count breaths if the cascading device ismanually advanced. The subject may take an additional breath to confirmthat the aroma has changed but will be asked to state the number ofbreaths taken before they actually noted the fresh aroma. The number ofbreaths is recorded for each nostril.

A battery of olfactory threshold testing for both nostrils may thus beperformed very quickly if a plurality of pure aromas are presented oneafter another, immediately after each fresh aroma is detected, ratherthan waiting for the subject to recognize that there is “clear air” orthe complete absence of aroma residual or latency.

Utilizing a cascading aroma method means that the newly presented aromaconcentration seems much stronger than any faint latent aroma fromprevious aromas, thus overcoming both human and mechanical latencyissues with the additional advantage of speeding up the testing processdramatically by abandoning a reset period between aroma events.

The plurality of pure aromas used may be placed in any order that putsthe most distinct odors between similar but different aromas to help thesubject differentiate between the aromas. Actual clinical testing hasbeen done cascading from 3 to 6 pure aromas with statistically similarresults.

Any number of aromas may be used as long as the aroma is advanced uponcognitive notice of the instant aroma. As few as two aromas may be usedalternatively, but 6 or even 8 completely different aromas in sequencemay be used with this method of testing. Completely changing the aromasis more far interesting to the subject than alternating between only twoor three aromas.

If, as in the previous example, using a 1.5 liter aroma chamber, thesubject averaged 10 seconds per aroma presentation, before cognitiverecognition of a fresh aroma had taken place, a complete test battery of10 events per nostril could be done on both nostrils in about 2 minutesor less.

Alternatively, rather than measuring a plurality of pure aroma detectionperiods in seconds, the number of breaths it takes to advance from thefirst aroma sequentially back to the first aroma is an alternativemetric. In other words, 25 breaths for the left and 18 breaths for theright is a meaningful scoring method. The breath tones sounds emittedare to allow supervision of the test procedure by clinical staffmembers.

The cognitive load factor is much less when the subject simply notesthat a new aroma is detected by pushing a momentary button to advance tothe next aroma, rather than remembering exactly what the aroma is andcognitively coming up with the name for it. Simply mashing a button uponnoting a fresh aroma has been smelled is very intuitive and easy tolearn.

Lacking an automatic aroma cascading mechanism, the device works tooffer an aroma by presenting 5 breaths, manually switch to a fresh aromaand handing the device back to the subject with the first aroma infusedin a volume of air in the chamber ready to be replaced by furtherinhalations. The number of breaths it takes to consume the first aromacontained in the aroma testing device until a fresh aroma is pumped upto the nostril indirectly increases the concentration of the fresh aromaas the first aroma cases away until cognitive notice is achieved. Theprocess is repeated for further aroma presentation events and theresults noted.

The Cascading Aromas Device

The described hand held aroma detection device present a much morelikely commercially viable embodiment of bilateral aroma testing forwidespread clinical use than the larger afore mentioned desktop units orpeanut butter and ruler as an apparatus. The handheld device,potentially removably clipped to a plaque on the wall of an examiningroom presents the notion of aroma testing being suitable for widespread,general clinical use as a neurological screening tool.

However, the aroma presentation device and aroma media might bedisposable, which has the advantage of using a sterile device for eachpatient, having a fresh device would eliminate latent aromas and thecost of a disposable screening device might be commercially moreprofitable than reusing it for multiple patients.

A multiple aroma cascade presentation device might be designed such thatthe test is self-administered. The person being tested would simply holdthe device comfortably up to their nostrils, close their eyes and pressa button on the handheld device to automatically advance to the nextaroma immediately upon noting the current aroma being presented to them.One first nasal cannula would present an aroma while the other secondcannula would provide clear air. The device might be symmetrical suchthat it only need be taken away from the nostrils and reversed to makethe second nostril the one presented aroma while the first nostrilreceives fresh air.

A series of tones could signal the starting point and ending point ofthe plurality of aroma presentations. A distinct audible tone, such as adinging sound, is sounded when the first aroma is presented and when thelast aroma is noted. The tones are to allow time interval measurement bythe clinical staff members as opposed to counting breaths.

A distinct “exhalation tone or honking noise” could indicate that abreath has been exhaled. The handheld aroma presentation device emits anaudible tone during exhalation to make the testing personnel aware ofthe breathing pattern of the subject.

A multiple chambered pure aroma or pure odorant cartridge may bemechanically spring loaded to advance in only one direction, one aromachamber at a time. The multi cavity aroma media is rotated intoalignment with a single airway communicating with the nostril, thedevice automatically advancing to the next aroma sample when actuated bypushing a control button.

With a hand held aroma presentation device without an aroma chamber, afirst aroma is presented and the subject is told to breathe normally andthen push a button conveniently located on the hand held aromapresentation device when they smell the aroma. A tone may be emitted bythe device as it advances to the second aroma and a visual readout wouldconfirm the aroma chamber in alignment with the airway for the testadministrator to observe.

A multiple chambered pure aroma or pure odorant cartridge may bemechanically spring loaded to advance in only one direction, one aromachamber at a time. The multi cavity aroma chamber is rotated intoalignment with a single airway communicating with the nostril, thedevice automatically advancing to the next aroma chamber when actuatedby pushing a control button.

A first aroma is presented and the subject is told to take 5 breaths andthen push a button conveniently located on the hand held aromapresentation device. A tone may be emitted by the device as it advancesto the second aroma and a visual readout would confirm the aroma chamberin alignment with the airway for the test administrator to observe.

Upon advancing sequentially though all the aromas, back to first aroma,pushing the button to indicate that the first aroma (and last) wasnoted, a discrete audible tone indicates that the first (and last) aromahas been noted. The time sequence is stopped at that instant, the periodin seconds between tones is the metric recorded for that nostril.

The timer may be a computer device, stop watch or a timer disposed andintegrated into the hand held aroma presentation device.

Alternatively, the aroma presentation device might be manually adjustedto present one aroma at a time for the counting of breaths to the pointof noticing a fresh aroma. The same device might also contain aplurality of aroma chambers such that an aroma identification test withmore than 20 aromas supported might be done with the device.

The number of seconds can be counted from the first breath taken throughthe plurality of aromas until the first aroma is recycled to the lastaroma, which is the stopping point of the test. For laboratory testingpurposes a simple gas flow meter might be placed in line with the airinlet port to confirm that a uniform flow of air is being inhaled foreach nostril being tested.

The number of seconds can be counted from the first breath to the breathwhere the fresh aroma is noted. For laboratory testing purposes a gasflow meter might be placed in line with the air inlet port to confirmthat a uniform flow of air is being inhaled for each nostril beingtested.

Dealing with Aroma Latency Issues

Such hand held aroma presentation devices that sequential offer pure airas opposed to aroma laden air and then reset back to pure air can havethe previously mentioned “mechanical aroma latency” issue.

When a slight hint of the single aroma being used is still detectable bythe test subject in the optimally pure air, it is a “mechanical aromalatency issue” as opposed to human latency factors.

Aroma latency in either form, mechanical or human aroma memory, nullifyor distort the testing perimeter. Mechanical aroma latency createsissues in accurate testing of subjects who can even slightly smell theprevious aroma for any reason in the clear air provided, before thedevice ought to deliver the aroma-infused air for a controlled testingevent.

Materials with a molecularly rough textured surface or a “high surfaceenergy” airway might tend to capture aroma molecules which may later bedetectable in the otherwise clear air. Thus, smooth surfaces and lowenergy surface are preferred to allow most aroma molecules to pass bywithout adhering to the airways of the device.

The mechanical aroma latency effect is exacerbated by potential humanodor memory, which makes one particularly sensitive to a singlepreviously smelled odor for a period of time that may be much greaterthan a 90 second reset period.

Overcoming both human and mechanical aroma latency issues in handheldaroma presentation devices are addressable in the following ways.

1. Reduce the aroma concentration and volume used as aroma sources tothe bare minimum amount of pure aroma required to accomplish the testfunction.

2. Using an ideal aroma formulation for the purpose of the test maymitigate mechanical aroma issue significantly.

3. Using a cascaded aroma testing method does not require a pureunscented air mode significantly nullifies the effect of trace amountsof latent, previously presented aroma as a second, stronger aroma masksthe far weaker previously presented, but still faintly latent previousaroma

4. Using a plurality of aromas without switching to a pure airpresentation will tend to also overcome human aroma latency by replacingthe latest aroma held in odor memory with a fresh aroma

5. Mechanical design minimizing surface areas exposed to aroma infusedair and special materials used in manufacturing hand held aromadetection devices would also tend to further mitigate mechanical aromalatency issues using materials that do not attract aroma.

6. Clear air pathways could pass through filtration or electrostaticplates to remove airborne aroma molecules

7. Using a disposable device allows a perfectly clean device for eachscreening

8. It may be possible to wash the device to remove old aroma adhered tothe parts.

Oleophobic airway parts and potentially even the device hollow body thatis exposed to aroma laden air could reduce significantly mechanicalaroma latency since “nothing sticks to teflon”. The aroma latency effectnullification by oleophobic materials is due to aroma molecules beingrepelled by such surfaces rather than being attracted by them, as is thecase with many common plastics, such as PVC. Having a low surface energyairway gives passing aroma no place to “stick” on a molecular level soit passes by without contaminating the surface of the airway.Manufacturing aroma devices where air pathways and potential the entireinterior of the device's hollow body are produced using a class ofoleophobic materials provide less aroma contamination potential. Thisclass of material will significantly reduce or practically eliminatemechanical aroma latency due to surface attraction of aroma molecules.

Lining air pathways with oleophobic interior coatings or using Teflonsurfaces in places exposed to aroma could thus dramatically reducemechanical aroma latency issues.

The non-exhaustive group of such preferred plastics and specialtymaterials that would tend to reduce the effect of capturing stray aromamolecules include; Teflon class plastics, silicone materials and anumber of oleophobic coatings and resins. Oleophobic coating and resinsmay be applied to metal, glass or ceramic hollow body surfaces used ashandheld aroma testing device hollow body parts or airways.

Some oleophobic resins require “firing” at up to 700 degrees F., whichwould preclude manufacturing aroma presentation devices with plasticsand using such resins. Further, the oleophobic effect of Teflon classplastics is fundamentally as strong as even the very best such resinsand coatings.

Teflon class plastics such as PFA (Perflouoroalkoxy), PTFE(Polytetrafluoroethelyne) and FEP (TetraFluorEthylene-Perfluorpropylene)may be obtained in clear, white or colors and may be extruded, injectionmolded, die stamped or blow molded, thus enabling preferred methods ofdevice mass production and support attractive industrial designs. Otherplastics having a relatively low surface energy, and thus likely torepeal aroma in contact with the material are, polystyrene,polyethylene, Tedlar, PVA, EVA and Acetal coatings of oleophobic resins.

Alternatively, rather than repelling aroma molecules using oleophobiccoatings or materials as mentioned above, electrostatic resins orelectrically charged plates could capture stray aroma molecules toprevent the clear air from being contaminated by latent aroma fromprevious aroma presentations.

The preferred materials and design embodiment for controlling latentaroma must clearly be repelling latent aroma molecules in the firstplace, rather than trapping them. Filtration media such as baking sodafilters or absorbent airway coatings, activated charcoal filtration,electrostatic filtering mechanisms and electrostatic resins allultimately reach a maximum aroma holding capacity and must be cleaned orfilters replaced to keep the aroma presentation device working asdesigned. This is not a preferred embodiment.

Oleophobic solutions would tend to minimize contamination of the deviceby aroma latency in the first place. Such devices would be much easierto clean, potential refreshed with a simple occasional wipe down with adisposable paper towel. Better to avoid the aroma contamination in thefirst place than to concentrate it in filters to control the pure aircontamination.

When a plurality of aromas are used, mechanical aroma latencycountermeasures as described above would largely prevent a detectablelatent aroma situation, since the newly presented aroma would be muchstronger than the previously offered aroma, a latent amount that mightbe only slightly detectable in clear air but not at all compared to afresh strong aroma.

Minimizing surface areas present less material to be contaminated. Sodesign can also mitigate aroma latency issues.

Multi-Aroma Chambered Devices

A hand held aroma presentation device might have a plurality of aromachambers, which can be mechanically rotated or selectively re-aligned ina way as to present an open pathway for only one aroma at a time. Such ahand held screening tool is a very desirable apparatus.

Aromas are presented sequentially while closing access to all otheraroma chambers. Such a device would speed up the testing proceduredramatically and reduce or eliminate significant aroma latency issues.

The person being tested would inhale through the aroma testing device tobring a plume of aroma infused air through only one of the plurality ofaroma chambers. The aroma passing through the device air pathways into anostril specula are presented directly into the test subject's nostril.

The improved hand held aroma presentation device described herein, mighthave 20 or more separate aroma chambers. Each chamber will selectivelyrotate in line with one airway port which is in fluid communication withthe nostril of the person being tested. Each aroma chamber has a feltlike pellet or disk held in place that holds a drop or more of aromafluid. The active airway draws air through the absorbent pellet or diskto infuse pure ambient air with an aroma.

The clinical employee or even the person being tested simply rotates anaroma presentation selector to align the single airway with the nextaroma in sequence. The device is advanced immediately upon the testsubject noting a fresh aroma was detected. When the number of screeningevents required are completed the cumulative elapsed time or number ofbreaths taken is recorded for each nostril and compared for a clinicallysignificant difference.

The same device may be used in scent identification where the aromas arenumbered such that the testing personnel can supervise the test as thesubject checks off one of 4 or 5 possible aromas they smell through thedevice. The device may then be reversed to check the other nostril as 20or more aroma are presented.

The aroma presentation device holds the multiple cavity aroma chamberpart in rotational alignment or in liner alignment with the hollow body.The segmented aroma chamber part or disk in one embodiment canpotentially only rotate or move in one direction to advance the aromasand clicks in place to mechanically allow the single airway path intothe hollow body to be aligned with only one of the aroma chambers at atime.

Ergonomically located on the exterior of the aroma testing device may bea button. The control button is mechanically disposed to swiftly advancethe aroma chamber to the next aroma upon the button being depressed. Atone may be emitted to denote advancement to the next aroma. A specialtone is emitted upon advancing from the first aroma to the second aromaetc. A digital or mechanical timer may be included which times theperiod from the second aroma being presented until that point cyclesagain.

The aroma chamber device may be spring loaded with a coil type spring, asmall motor or other mechanical device which upon the button beingpushed advances the aroma chamber to the next station. Ratcheting gearsknown to the art may be employed to insure that the aroma chamber onlyadvances in one direction. The audible tones may be electronic ormechanical with one tone to denote each new aroma as it is presented anda second distinctive tone is emitted at the presentation of aroma #1when it appears as the final aroma.

The exhalation airway is arranged such that an audible tone is emittedwhenever the test subject exhales. The number of exhalations required tocomplete the test may be a metric of some interest. The number ofbreaths for each nostril may also be helpful in insuring that the personwas breathing equally through each nostril and not hyperventilating.

Each multi-cavity aroma cartridge comprises separate chambers forholding at least two odorants or pure odorants, one odorant or pureodorant per chamber, but may hold 20 or more odorants, pure odorants.

Using the proposed rapid presentation or cascade of a plurality of purearomas as a testing perimeter and metric also solves the problem ofclearing the aroma testing device chamber and pure air pathway of asingle aroma to return it to a clear air mode in preparation for thenext aroma presentation testing event. This issue is seen mostprofoundly in the clear air vs single aroma mode of testing.

The sequential aroma cascade method simply does away with the clear airmode entirely in favor of effectively resetting the olfactory nerve bypresenting a fresh aroma through the faster olfactory “reset” phenomenonof sensory dissonance.

Using the plurality of sequentially presented aromas as a testing methodactually simplifies the mechanical device required to present the aromasand manage the testing events. Not being required to revert to a clearair mode between testing events nullifies the need for a number of partsin many embodiments of previous handheld aroma testing devices usingonly one aroma. Devices with a plurality of aromas also does away withthe requirement of a large aroma chamber in favor of simply passingclear air through a plurality of aroma containing felt like elements.

A removable multi-chambered aroma element could be sold as a consumabletest element allowing for an easy way to refresh the device. After oneor more aroma tests have exhausted the rotating aroma multiple cavitycartridge or disk, is disposable. The replaceable cartridge or diskcontains a plurality of fresh pure aromas especially formulated at thefactory to work well with the aroma presentation device. Seals coveringports in the multi cavity aroma chamber are removed and the fresh aromacartridge is installed. Alternatively, the entire device is disposable.The aroma media disk disclosed may use actual essential oils andpreserve them for a considerable shelf life due to release stripssealing the aroma in a small chamber holding an absorbent felt likemember that allows air flow through it to infuse air with the aroma.

FIGS. 1-3 provide a housing 10 and a cap 200. Housing 10 comprises a toplip 12 defining an inner shoulder 14 and outer threads 16. Housingfurther defines inner air chamber 18 having an air inlet 20 disposedtherethrough that may be located on bottom surface 22 of housing 10.Bottom surface 22 of housing 10 may further comprise an connectionaperture 24.

The embodiments of FIGS. 1-3 further comprise an upper gasket 28,affixed to the outer lower surface 26 of the housing 20 and comprising ashape generally the same as the shape of the housing's lower surface 26and further comprising air inlet aperture 30 and connection aperture 32therethrough. Air inlet aperture 30 matches and is aligned with the airinlet 20, allowing fluid communication therethrough while connectionaperture 32 matches and is aligned with connection aperture 24.

The embodiment shown in FIG. 1 further comprises an advancer mechanism40 that comprises an upper surface and a lower surface, wherein theupper surface is attached to the upper gasket 28 and may compriseadvancer button 42. As shown in FIGS. 6A and 6B, advancer mechanism 40may comprise a ratcheted gear mechanism 44 as is well known in the art,or alternatively, a wound spring mechanism 46, or clock springmechanism, as is also well known to the skilled artisan. These exemplarymechanisms ensure that, when advanced by actuating the advancer button42, the pure odorant or pure aroma cartridge advances in only onedirection. Advancer mechanism 40 comprises an air inlet aperture 47 anda connector aperture 48, wherein air inlet aperture 47 is matched andaligned with air inlet aperture 30 of upper gasket and connectoraperture 48 is matched and aligned with connection aperture 32 of uppergasket.

The embodiment of FIG. 1 further comprises a lower gasket 50, affixed tothe lower surface of advancer mechanism 40 and comprising the same orsimilar features as the upper gasket 28, i.e., an air inlet aperture 52and connection aperture 54, wherein air inlet aperture 52 matches withair inlet aperture 47 of advancer mechanism 40 and connection aperture54 matches and is aligned with connection aperture 48 of advancermechanism 40.

The embodiments of FIGS. 1-3 comprise a pure odorant cartridge 60 thatis rotatably affixed to the lower surface of lower gasket 50 andcomprises at least two odorant chambers 62. The embodiment of FIG. 1further comprises the odorant chambers 62 being capable of rotating intoindividual fluid communication with air inlet aperture 52 of lowergasket 50.

For each illustrated embodiment of FIGS. 1-3, and as shown in FIGS. 5Aand 5B, six or eight, or any other number larger than one, odorantchambers 62 are provided. Pure odorant cartridge 60 may comprise acentral axis 64 around which the rotatable pure odorant cartridge 60rotates.

Central axis 64 comprises a top connector 66 which is rotatably alignedwithin connector apertures 52, 48, 32 and 24 in the embodiment of FIG.1.

Top connector 66 thus engages connector apertures 52, 48, 32 and 24providing a snug fit of all components described above against lowersurface of housing. Application of sufficient downward force willovercome the engagement of the top connector 66, thereby allowing thepure odorant cartridge 60 to be removed. Consequently, it is possible toreload a spent pure odorant cartridge 60 and replace it withre-engagement of top connector 66 with connector apertures 52, 48, 32and 24. Alternatively, a pure odorant cartridge 60 that was previouslyloaded with pure odorant in odorant chambers 62 may be engaged withconnector apertures 52, 48, 32 and 24. The embodiments in FIGS. 2 and 3do not require advancer mechanism 40 or lower gasket 50.

Lower surface LS and in some embodiments, upper surface 68, of pureodorant cartridge 60 may be covered with an adhesive layer 70 comprisingvalves 72 aligned with the pure odorant chambers 62 as in FIG. 7A.Valves 72 may comprise resilient flaps 73 cut through the valvematerial, e.g., silicone or rubber, to allow air flow therethrough. Thislayer prevents escape of the pure odorant within the chambers 62, butallows air flow therethrough. Alternatively, individual valve elements72A, generally of the same construct as layer valves 72, may be providedas illustrated in FIG. 7B. Such valve elements may comprise an outeradhesive portion 74 to cover the related chamber 62.

Pure odorant cartridge 60 may rotate by aid of the advancer mechanism 40described above or, alternatively, advancer mechanism 40 may be bypassedor be eliminated altogether. See, e.g., FIGS. 2 and 3 for manuallyrotatably advanceable embodiments. In either case, pure odorantcartridge 60 may be rotatably advanced manually, aligning an initialpure aroma chamber 62 with air inlet aperture 52 of lower gasket 50.

With reference to FIGS. 1-3, cap 200 comprises a body 201 defining achamber 202 therein, a nasal port 204 and nasal port lumen 206 withinnasal port 204, wherein nasal port 204 is in fluid communication withchamber 202 and with the atmosphere outside the nasal port 204. Nasalport 204 may be covered by a removable nasal specula 205 or theequivalent.

Cap 200 further comprises threads 207 that are capable of threadedcommunication with outer threads 16 of housing. Other methods andmechanisms for joining the cap 200 with the housing 10 are certainlywithin the scope of the present invention. Moreover, an alternateone-piece construction with cap merged with housing is also within thescope of the present invention. Cap 200 further defines at least oneexhalation valve opening 208 through the cap body 201 which is shownwith a resilient valve 210 disposed over the at least one valve opening208.

FIG. 4 illustrates a flap valve 212, having a lip 214 that rests onhousing's inner shoulder 14 is provided. As known in the art, oneportion of the flap valve is fixed to the inner shoulder 14, whileanother portion of flap valve 212 is moveably disposed on the innershoulder 14. This arrangement allows air flow with sufficient force tolift the moveably disposed portion of the flap valve 212 upward from thehousing to the cap and nasal port. It also prevents downward air flowfrom the nasal port and cap into the housing.

Accordingly, an exhalation air flow path is provided within cap as bestillustrated in FIG. 2. There, a patient exhales through the nasal port204 into the cap chamber 202 and out of exhalation valve opening 208, asthe downward air flow is blocked and redirected by the closed flap valve212. Alternatively, the patient may simply disengage the nostril fromthe nasal port 204, exhale into the atmosphere and then reengage thenostril with the nasal port 204 for a second inhalation.

FIG. 3 illustrates the active inhalation air flow path, initiated by apatient inhaling through nasal port 204 with sufficient force to enablethe active path. Here, external atmospheric air flows inwardly throughthe valve members 72 or 72A in alternative embodiments, and into thepure odorant chamber 62 aligned therewith. The pure odorant mediatherein infuses the incoming air with the pure odorant aroma and theinfused air flows through the aligned air inlet apertures and into thehousing chamber 18. The infused air flow pressure raises the flap valve212 to enable the infused air to flow into the cap chamber 202 and outof the nasal port 204 into the patient's nostril.

Thus, this exemplary device may be used to present a more than one pureodorant in a cascading fashion, i.e., sequentially and within a resetperiod between presentations. Initially, a first pure odorant is madeavailable for presentation to one nostril of a patient, wherein thepatent inhales to activate the inhalation air flow pathing describedabove, and exhales into the device until a fixed number of breaths arereached, or a fixed time has elapsed or until the patient recognizesthey have reached the pure odorant detection threshold, whereupon therelevant metric is observed and recorded. At this point, themulti-chamber pure odorant cartridge 60 is advanced to the next pureodorant and the process is repeated and again if additional pureodorants are provided in the testing process and in the cartridge 60.

When the first nostril testing is completed, the same process isrepeated with the second nostril. Ultimately, the results are compiledand the left nostril and right nostril data is compared for substantialdifferences between the left and right nostril data sets.

FIGS. 8A-8C illustrate another embodiment comprising an aroma screeningdevice 300 using an off-the-shelf glass jar with a threaded lid as abase. Lid assembly 302 comprises a die cut slip ring 304 incommunication with a plastic top member 306 having a series of apertures308A, 308B, 308C therethrough. Nasal port element 310 comprises a nasalport 312 therethrough which engages one of the apertures 308B. Nasalport element 310 is operationally engaged with plastic top member 306and with plastic lower member 312 which comprises holes therethrough314A, 314B. 314A is in fluid communication with the nasal port 312. Atube 316 is provided, having a proximal end 317 in fixed attachment,e.g., glued, to the plastic lower member 312, wherein the lumen 320 oftube 316 is in fluid communication with nasal port 312 and hole 314B.Distal end of tube 318 is in fixed attachment with the pure odorantchamber cover element 322 which comprises a hole 324 therethrough influid communication with tube lumen 320, a pure odorant chamber accessaperture 326 and a pure odorant release aperture 328 disposed on a side330 of the pure odorant cover element 322. Pure odorant cover element322 covers pure odorant cartridge 332 which is fixed in place at thebottom of the jar. The entire assembly, aside from the fixed-in-placecartridge 332, is capable of rotation from one pure odorant media 336within a chamber 334 within cartridge 332 to the next, or another, pureodorant media 336 within chamber 334.

Thus, a nasal port 312 is in rotatable fluid communication with a pureodorant cartridge 332 comprising at least two pure odorant chambers 334each capable of holding a single pure odorant medium 336. A centralinhalation tube 316 in valved communication with the atmosphere and withone of the pure odorant chambers 334 when the nasal port 312 isrotatably aligned with the desired pure odorant chamber 334. Anexhalation path is provided as illustrated that flows downward throughthe valve and into the central tube 316, through the pure odorant media336 within the aligned pure odorant chamber 334, infusing the inhaledair with the aligned pure odorant aroma. The infused air then flowupwardly through the nasal port 312 and into the patient's nostril untilthe patient signals reaching the pure odorant detection threshold or, incertain embodiments a maximum number of breaths and/or time is reached.Rotation of the lid assembly to another pure odorant chamber 334 allowsrepeat of the process without a reset period, i.e., cascading of pureodorants.

Turning now to FIGS. 9A-9C, another embodiment of a multiple aromapresentation device 400 is provided and comprising a (preferably) glasshousing 402 defining a chamber 404 therein having an open top edge 406and a lid assembly 410 that is fixed to the top edge 406 of the glasshousing 402.

The lid assembly 410 comprises a jar lid 412 with a generally centralstem opening 414 therethrough and a generally off-center air inlet port416 therethrough covered by flap valve 417, shown removed from coveringport 416 for illustrative purposes.

Lid assembly 410 further comprises a nasal tip 418 having a lumen 419therethrough and aligned with the generally central stem opening 414 andin fluid communication thereof. Nasal tip 418 further comprises one ormore exhalation ports 420, each of which are in fluid communication withthe nasal tip lumen 419. The exhalation port(s) 420 are covered by aflexible circumferential valve member 422 which works as a one way valveto allow exhaled air to exit the device into the atmosphere but notallow ambient air into the device. For example, a rubber band type valvemember may be used. Other equivalent valves will present themselves tothe skilled artisan, each of which are within the scope of the presentinvention.

The pure odorant cartridge 430 comprises more than two pure odorantchambers 432 therein. The cartridge 430 is preferably circular in shapewith the odorant chambers 432 arranged circumferentially. In theillustrated embodiment, eight chambers 432 are provided. A stem 434 witha lumen 436 therethrough is disposed fixedly generally centered on thecartridge 430. Stem 434 rises above the top surface T of the cartridge430, engages the stem opening 414 of the jar lid 412 and is in fixedoperational engagement with the nasal tip 418 and stem lumen 436 is influid communication with nasal tip lumen 419 and glass housing chamber404. As illustrated, the nasal tip 418 might threaded for threadedengagement to the stem 434, or be otherwise fixable attached to the stem434.

In a preferred embodiment, each chamber 432 holds a single pure odorantor aroma pellet 436 which is a cylindrical shape matching the shape ofthe chambers 432 in the cartridge 430. The pure odorant pellets 436 arepreferably composed of absorbent material such as felt or cotton whichwill allow air to pass through and expose the inhaled air flow to afluid aroma source soaked up by the absorbent material.

Lid assembly 410 further comprises a gasket 438 held between the bottomsurface S of the cartridge 430 and a retaining disk 440 describedfurther below. The gasket 438 preferably comprises a soft silicone likematerial which may have a shore hardness of about 40 with a thickness ofabout 0.125 inches, though other materials, hardnesses and/orthicknesses are within the scope of the invention. The gasket 438 allowsthe cartridge 430 to be rotated without opening undesired airwaysbetween the pure odorant chambers 432 and the inhalation air path whichwill be discussed infra. The gasket 438 have comprise holes forfasteners, e.g., screws, to pass through that hold the retaining diskand jar lid together such that the cartridge 430 is held snuggly butallowed to rotate in place. Gasket 438 comprises a flap valve 442aligned with the air inlet port 416 and a flap valve 444 aligned withthe stem lumen 436, as illustrated, each of which operate as a one wayvalve to enable air flow. Other one-way valve solutions will becomeapparent to the skilled artisan, each of which are within the scope ofthe present invention.

Lid assembly 410 further comprises a retaining disk 440 as describedabove that is attached to the gasket 438 and works to retain thecartridge 430 in such a way as to allow the cartridge 430 to rotatefreely, but not translate vertically. The stem 434 engages and extendsthrough the stem opening 414 such that rotating the stem 434 rotates thecartridge 430 and, therefore, is adapted to enable alignment of any ofthe plurality of pure odorant media, e.g., pellets, held in the chambers432. The retaining disk 440 comprises an indexing bump 450 or otherindexing feature on the upper surface that fits into the bottom of anyone of the chambers 432 to enable alignment with a particular chamber432. Retaining disk 440 further comprises a central orifice or orifices452 aligned with the flap valve 444 of gasket 438 as well as acircumferential orifice 454 that is aligned with the flap valve 442 ofgasket 438.

Finally, lid assembly 410 further comprises a dip tube 460 fixedcentrally on the bottom surface B of the retaining disk 440 andcomprising a lumen 461 therethrough. The dip tube 460 may be glued inplace and is in fluid communication with the stem lumen 436 and nasaltip lumen 419 as well as the glass housing chamber 404. Further, or inthe alternative, a nipple 462 may be fixed on the center bottom B of theretaining disk 440 that holds, or assists in holding, the dip tube 460in place. The dip tube 460 may be an extruded plastic tube that repelsaroma, such as Teflon.

The interior surfaces of the device may be coated with an aromarepellant material to help control mechanical latency due to a build-upof aroma molecules on internal airways. One such molecularly repellantmaterial has been invented at Harvard University. It is anticipated thatsuper repellant materials might exceed the ability of oleophobicmaterials such as Teflon by up to 20 times the capacity of low energyplastics.

Thus, a cascading of pure odorants may be achieved, without a resetperiod between presentations of the different odorants. As shown inFIGS. 9A and 9B, the cartridge is preloaded with at least two pureodorants 436. The illustrated cartridge 430 comprises eight chambers 432for pure odorants. The desired first pure odorant chamber 432, withdesired first pure odorant 436 therein, is aligned with the inlet port416 of the jar lid by rotating the lid assembly 410. The subject thenengages the nasal tip with a nostril and inhales, thereby initiating aninhalation air flow wherein atmospheric air enters the jar housing atthe air inlet port, passing through the air inlet valve, through thefirst pure odorant chamber 432, where the inhaled air becomes infusedwith pure odorant. The infused air then passes through the flap valve ofthe gasket 438 and the orifice of the retaining disk 440 and then entersthe dip tube 460. The infused air flows upwardly through the dip tube460 and through the nasal tip lumen into the subject's nostril where theinfused air is inhaled and cognitive processing begins. The subject mayexhale directly into the nasal tip where, as shown in FIG. 9C, thecircumferential valve allows the exhaled air to release into theatmosphere. The subject then inhales air infused with the first pureodorant again. The process is repeated until the patient signifiesachieving the pure odorant detection threshold. The cartridge is rotatedto the next pure odorant in the test and the inhalation/exhalationprocess is repeated until reaching the pure odorant detection threshold.The metric measuring the reaching of the detection threshold may bemeasured in number of breaths and/or in time.

Turning now to FIGS. 10A-13B, a pure odorant presentation device 500 isprovided that supports an exchangeable pure odorant cartridge 501containing at least two pure odorants for various scent testingpurposes. The device 500 consists of an openable body 502, e.g., hingedand capable of holding the pure odorant cartridge 501, a dual nostrilport 504 comprising an active nasal path and a passive nasal path,capable of engaging left and right nostrils of a subject at the sametime, an optional internal cartridge rotational system which may bebutton actuated. Alternatively the cartridge 501 may be manuallyadvanced. An advancement button 508 capable of actuating advancement, areadout means to display aroma information to testing personnel and anaroma media disk rotation control button. The active nasal path enablesfluid communication between a first nostril, engaged with the nostrilport 504, and a selected and designated pure odorant while the passivenasal path enables fluid communication between the second nostril andthe atmosphere.

FIG. 10A illustrates one embodiment of the device 500 with active, i.e.,pure odorant infused airflow, left nostril pathing and passive (noodorant infused air) pathing for the right nostril. FIG. 10B illustratesthe device 500 of FIG. 10A rotated 180 degrees so that the right nostrilpath is active and the left nostril path is passive.

The exchangeable odorant or pure odorant cartridge or aroma media disk501 consists of a rigid central body 510 which may be approximately thesize of a standard CD Rom used with computers. The central body 510 hasa hub hole 513 that is indexed to cause one pure odorant chamber 512containing pure odorant media, e.g., an absorbent pad or pellet 514, ata time to be aligned with internal airways. The central disk has atleast two chambers 512 designed to support absorbent pads or pellets 514which may progressively be aligned with airways. The chambers 512 may bedesigned with an offset or air gap 516 to prevent capillary actionallowing liquid aroma containing fluid to leak out of the chamber 512.

An embodiment of the cartridge 501 is illustrated in FIGS. 11A-11C and12A-12F, including illustration of insertion of a pure odorant media 514into a chamber 512. FIG. 12 provides a side exploded view of thematerials and structure of one embodiment of the cartridge 501. Oneither side of the central body 510 are silicone or similar materialdisks 520A, 510B, adhesively attached to the central body 510. The firstand second silicone disks 520A, 520B, each have a hub hole 522 in thecenter matching the hub hole 513 in the central body 510 and a die cutslot 524 functioning essentially as a valve that passes over the pureodorant chambers 512 such that the slot 524 passively covers all thepure odorant media therein. This slot 524 is best seen in FIG. 11A.

Thus, when air is forced against the first flexible silicone disk 520A,air is forced through the slot 524 and allowed to flow through the aromainfused pure odorant media, e.g., pad or pellet, to create pure odorantinfused air which is forced through the slot 524 on the second siliconedisk and into active airway whereby the aroma infused air is ducted intothe active cannula to be inhaled by the test subject. When air is notpassing through a given chamber 512, the silicone material returns to apassive sealing position. The silicone disks are permanently attached tothe central disk trapping the absorbent pads in place.

On the outer surface of both silicone disks is a release strip 530A,530B which covers both sides of the cartridge 501, i.e., covering thefirst and second silicone disks 520A, 520B and the slots 524 therein,such that they must be removed to load the cartridge 501 into the aromapresentation device body.

FIGS. 13A-13C provide illustration of the airflows in the device duringoperation. FIG. 13A illustrates the active nostril pathway, withatmospheric air passing through a one-way valve 540 to teach the firstsilicone disk 520A and slot 524 therein. The air passes into thedesignated and aligned odorant or pure odorant chamber, with pureodorant media therein, where the air becomes infused with the odorant orpure odorant disposed within the aligned chamber. The air flow continuesas the odorant or pure odorant-infused air flows through the slot 524 inthe second silicone disk 520B and upward past one-way valve 542 andthrough the nasal port 504 into the active first nostril. Meanwhile, thepassive second nostril is in fluid communication with atmosphere asshown in FIG. 13C. Finally, the active first nostril comprises anexhalation path as in 13 B where the active first nostril exhales airinto the nasal port 504 where it opens one way valve 542 and exits thedevice 500 to the atmosphere.

FIGS. 14A-14C further illustrate the device of FIGS. 10A-13C. Thus,cartridge 501 is provided as described previously. In this embodiment,however, the hub hole 513 is non-circular. Specifically, a keyedgeometry is employed for hub hole 513 to enable engagement with, e.g.,the advancer mechanisms discussed supra, see, e.g., FIGS. 6A (ratchetedgears) and 6B (wound spring or clock spring) for specific examples.

Turning now to FIGS. 15A and 15B, a side cutaway view of the cartridge501 of FIGS. 13A-13B is illustrated. Thus, the active odorant or pureodorant pathway and the passive pathway are clearly illustrated.Finally, FIGS. 16A and 16B provides a side and front view of the device500, with advancer button 508 and rotated so that the active pathway ison the left nostril port 504B. Indication of the active pathway nostrilport is provided on the front of the device as “Left”. Turning thedevice 180 degrees provides the active pathway on the right nostril port504A and indication of same is provided on the then-front of the device(not shown) as “Right”. Further, an indexing indicia is provided withthe device 500 to enable tracking of the specific odorant or pureodorant under current presentation to the patient. The exemplar in FIG.16B indicates “12” which is associated with a specific odorant or pureodorant chamber in the cartridge 501. A key will be easily provided thatmatches the indexing indicia with the odorant or pure odorant currentlyresiding within the chamber that is associated with indicia “12”. Thus,each chamber will comprise a related indexing indicia which providesannunciation of the chamber under consideration and, therefore, theodorant or pure odorant, being introduced to the patient.

Note that the methods, devices and systems disclosed herein have utilityfor pure odorants in the measurement of bilateral pure odorant detectionthresholds. These devices also may be used for any odorant, includingpure or non-pure odorants. In other words, odorants that also stimulatethe trigeminal nerve (non-pure) may also be used with the discloseddevices and methods.

In the case of non-pure odorants, the metric used will comprise anodorant identification threshold. Thus, the patient will be presentedwith the odorant-infused air as described above for pure odorant-infusedair, and the next odorant sequentially introduced as soon as the patientidentifies the first odorant by name. This identification point isdefined herein as the odorant detection threshold. Preferably, theodorants' sequential presentation using the described devices andmethods is done without a reset period between odorant introductions.

Working Example 1

In an initial study, a single nostril aroma testing device was used. Thedevice was one liter in capacity and was used with 31 participants. Theages of those tested ranged from 15 to 84. The participants varied as toeducational achievement from high school dropouts to a medical doctor.Socially the group consisted of a multimillionaire, a box boy, a highschool student, several RNs and a number of retired people.

The metric of testing was cascading a set of pure odorants in anintroduction sequence and counting breaths between the introduction of afresh aroma and the participant recognizing the fresh aroma, i.e.,reaching the pure odorant detection threshold. Alternatively, the timerequired to reach the pure odorant detection threshold may have beenrecorded.

The pure odorants used were applied in sequence, i.e., cascaded, withouta reset period between successive introductions of the odorants andaccording to the following key for the randomly selected right nostrilfirst:

R1: Lemon (Citrus family);

R2: Rose (Floral family);

R3: Spearmint (Herbal family);

R4: Cinnamon (Spice family);

R5: Clove (Spice family); and

R6: Vanilla (Spice family).

Followed by the left nostril:

L1: Lemon (Citrus family);

L2: Rose (Floral family);

L3: Spearmint (Herbal family);

L4: Cinnamon (Spice family);

L5: Clove (Spice family); and

L6: Vanilla (Spice family).

The summary data is provided in Table 1.

TABLE 1 Patient ID Right Nostril Total Breaths Left Nostril TotalBreaths 1 27 29 2 16 13 3 22 19 4 27 20 5 21 22 6 28 21 7 17 24 8 24 229 18 14 10 18 21 11 20 18 12 19 34 13 16 21 14 20 19 15 25 23 16 35 2517 19 29 18 17 18 19 18 20 20 17 14 21 15 17 22 18 20 23 20 20 24 26 3625 14 12 26 18 18

Analysis:

The average number of breaths across all participants was around 4breaths per aroma event. Those with poor lung capacity or shallowbreaths tended to require 5 or 6 breaths as opposed to athletes withgreater lung capacity who only required 2 breaths.

One of the participants (patient 17) was a known victim of Alzheimer'sdisease as confirmed by alternative means. As predicted, patient 17 hada significantly lower aroma sensitivity on the left nostril compare tothe right nostril. Three participants (patients 7, 12 and 13)demonstrated a marked deficiency of the left nostril as compared to theright without any other likely cause than AD.

The remaining patients may, using this test method, be ruled out forAlzheimer's disease.

Thus, the data show that using the number of breaths required torecognize that the aroma presented has changed renders usefulinformation formative in assessing the relative condition bilateral ofthe olfactory nerve. While overall scent sensitivity may be impacted, itis thought deterioration due to environmental issues such as chemicalexposure are likely to affect both nostrils similarly. The thing beingtested is the relative sensitivity of the nostrils not the absolutesensitivity. Some people have a stronger sense of smell than others butone side being significantly weaker only affected roughly 10% of thosetested.

Using the cascading aroma method the number of breaths or seconds usedas a scoring metric, required to recognize a fresh aroma is beingpresented are less for a strong sense of smell and more for a weakersense of smell. Sometimes the subject would take more breaths to makesure they really did smell a fresh aroma. Those with particularly strongsensitivity were more certain the aroma was changed without morebreaths.

Laboratory testing to verify assumptions behind the testing protocol canbe done to satisfy scientific scrutiny. The aroma screen can bevalidated in a number of ways related to various metrics and methods ofaroma presentation and the indirect and direct measurement of pure aromaconcentration required to illicit a cognitive trigger that an aroma hasbeen smelled in one nostril. Comparison alternative screening methodsstatistically validates a screening method if both consistently render asimilar result.

1. A gas flow meter may be hooked up to the intake port of the device toconfirm that a relativity equal rate of inhalation is used over thecourse of a screening.

2. The number of seconds and the number of breaths are thought to bestatistically similar, but can easily be recorded together to confirmstatistical similarity.

3. Counting breaths from the point in time a pure aroma was changed tothe next aroma in a sequence can be validated as consistent with theconcentration of pure aroma seen at the nostril with an electronic nosedevice in a lab.

Using the proposed rapid presentation or cascade of a plurality of purearomas as a testing perimeter and metric also solves the problem ofclearing the aroma testing device chamber and pure air pathway of asingle aroma to return it to a clear air mode in preparation for thenext aroma presentation testing event.

The sequential aroma cascade method simply does away with the clear airmode entirely in favor of effectively resetting the olfactory nerve bypresenting a fresh aroma.

Using the plurality of sequentially presented aromas as a testing methodactually simplifies the mechanical device required to present the aromasand manage the testing events. Not being required to revert to a clearair mode between testing events nullifies the need for a number of partsin many embodiments of handheld aroma testing devices.

A removable multi-chambered aroma element could be sold as a consumabletest element allowing for an easy way to refresh the device. After anumber of aroma tests have exhausted the rotating aroma multiple cavitycartridge, it is disposable. The replaceable cartridge contains aplurality of fresh pure aromas especially formulated at the factory towork well with the aroma presentation device. Seals covering ports inthe multi cavity aroma chamber are removed and the fresh aroma cartridgeis installed.

Generally speaking, contamination of the pure odorants with anyadditional additives or ingredients that might also excite thetrigeminal system should be avoided. In addition, common commercialaroma “essential oil” bases and preservatives might tend to coat theairways of the aroma chamber and gas pathways with commercial aroma baseoil materials, creating an aroma latency failure mode even where theclear air may be slightly contaminated with aroma. Thus, pure aromamaterials used in the test may be better diluted with water or traceamounts of alcohol which would evaporate and not leave a latent odor onthe interior surfaces of the testing device. Additionally, the lowestconcentration and amount of aroma that is still detectable by the userwill reduce aroma latency on the air pathways of the device. Certaincoatings on the inner surfaces of the devices disclosed herein may alsotend to repel the aroma molecules instead of presenting a surface towhich the aroma molecules adhere. Alternatively, lining the interior ofthe aroma presentation device with an electrostatic mat might captureand hold aroma molecules to maintain a clear air pathway withoutcontamination of the pure air. Such material can be washed off torecharge the electrostatic resins use in such products as furnace airfilters.

A computerized application and alternative embodiment of the method maybe provided. Here, the data may be entered by hand into a spreadsheetpreviously created and saved within the memory of a programmablecomputing device, accessory or appliance such as previously described ormay be automatically communicated by, e.g., a USB device as describedherein that is connected to the testing device and in communication,i.e., wired or wireless, with the computing device. In addition, thecomputing device can control the testing device in terms of stopping andstarting aroma presentations.

Moreover, a software database and testing protocol supportapplication(s) may be used to achieve the testing described herein withany of the disclosed device and system embodiments of the presentinvention. The software database may be within individual computingdevices and/or may be housed within a central server that isinterconnected with individual computing devices that are located attesting sites. As illustrated, at least one central server is providedand in communication with at least one remotely located computingdevice. Central server(s) may be cloud-based which may permit controlledaccess from any internet connected device, preferably a secure accountenabled internet connection is employed.

Thus, a programmable computing device for implementing the invention maycomprise: a memory, wherein the application, including programmedinstructions for running the test protocol embodiments described hereinis stored and for storing test results; a processor operativelyconnected with the memory and which executes the application andassociated programmed instructions; a display that may display theapplication, test data results for left and for right nostril trials,trial number, a timer and the final calculated results in terms of anydifferential between the left and the right nostril detectionthresholds, or a differential between a previous baseline or populationstatistical average score, and the instant test score. The display isoperatively connected with the processor and memory; and a transmitterand a receiver for operatively connecting, and communicating with, thecentral server. In this system, the testing results may be obtained atthe testing sites and added, either manually or automatically asdescribed herein, to the computing device for storage and possibletransmission of the data to the central server.

When the testing procedure is complete, the test data may be sent,either automatically or upon prompting by the user, from the computingdevice at the associated test site to the remote central server. Centralserver comprises a memory for storing the received test data from the atleast one computing device and associate test site(s) and for storing analgorithm for processing and analyzing the instant test site results; aprocessor for executing the programmed instructions within the storedalgorithm; a transmitter and a receiver operatively connected with theat least one computing device whereby two-way communication with the atleast one computing device is enabled. Central server's memory furthercomprises a database for storing all of the test results received fromthe at least one computing device which may be used to develop furtherrefined and more robust statistical conclusions regarding relevantelements of the patient's medical history and the instant test datareceived from the at least one computing device for an individualpatient and securely transmit the calculated disease risk score based atleast in in part upon global data stored within the memory of thecentral server and reported to the local computing device. Robustencryption and security features may be employed to protect individualpatient's privacy rights.

This refinement will thus enable, e.g., a progressively more robust testresult that may allow detection of a significant differential or changein the test data for an individual patient. For example, early onset ofAlzheimer's disease may be detected progressively earlier as thedatabase becomes more populated to eventually become a vast library ofrelevant medical history and patient test data and, as a result, becomesmore robust. Thus, certain embodiments of the database of the centralserver may allow analysis of the data within the database for generationof the smallest possible differential in the olfactory threshold values,left vs right, that is still clinically significant. This is the pointat which the device, systems and methods of the present invention willallow earliest possible detection of asymmetry and, in turn, earliestpossible detection of Alzheimer's disease.

Similarly, in the case of symmetrical olfactory dysfunction, thedatabase of the central server may be analyzed to determine the smallestchange, from either baseline or from a prior test point or from apopulation statistical average, that may be considered clinicallysignificant. This represents the finest analysis and diagnosis possiblefor symmetric olfactory dysfunction and the ability to monitor theunderlying condition or disease progression and/or the efficacy of thetreatment regimen.

The algorithm of the central server may analyze the data received fromthe at least one computing device and, when analysis is complete, thecentral server may transmit an electronically secure summary of thetesting results as a risk score as described above back to the computingdevice at the test site so that the user, i.e., a health care provider,can observe the results by, for example, a secure email sent to apredetermined email address.

In addition, a separate application or, alternatively, an internetbrowser supported client program may supply a checklist of a patient'spre-testing history and enable establishing of the patient's clinicallyacceptable baseline of nasal performance, including any relevant medicalhistory factors such as structural or medical issues that may compromisethe left or the right nostril/airway performance and/or efficiency. Thisbaseline value may be incorporated into the above algorithm to provide acorrective factor that essentially treats any observed airwayperformance for the left and/or right nostril and associated airway as avariable that may skew the final results if not corrected. The databasedescribed above may also accept input of this data and incorporate itinto the analysis phase to enable a corrected result to be calculatedand typically securely communicated to the appropriate computing deviceand associated test site.

As described above, certain embodiments of the disclosed devices of thepresent invention comprise measurement of the concentration of theodorant, or pure odorant, presented to the patient's nostrils that arerequired to evoke a response by the patient, i.e., an indication thatthe pure odorant detection threshold was reached.

Still further embodiments may capture the number of breaths a patientrequires to inhale through the various devices and methods of thepresent invention to reach the olfactory threshold for each nostril. Thebreath data may be captured and analyzed for example, by the computingdevice application and/or at the central server(s) as described above.

A combination of data types may be obtained using the devices andmethods of the present invention, e.g., capturing the elapsed timebetween introducing aroma to the aroma airway passage and the detectionthereof by the patient, the number of breaths required to detect theintroduced aroma and/or the absolute concentration of odorant, or pureodorant, required to reach the olfactory threshold for each nostril. Thedata may be analyzed by the local computing device's application and/oranalyzed remotely at the central server(s) as described above in orderto determine the patient's odorant, or pure odorant, detectionthreshold.

In certain embodiments, the testing protocol may be accomplished usingthe various devices and systems of the present invention described aboveby slowly increasing the concentration of aroma until the trigger pointof cognitive notice is reached. This may be done by measuring the timeit takes to recognize an increasing aroma level. Similarly, the numberof inhalations required during a testing event required to detect thearoma may be significant, simple and useful measurable standard.

In an alternative embodiment, an absolute aroma concentration testingmethod, a real time digital “electronic nose” measurement of the actualparts per million of pure aroma per a known volume of breathable gas maybe used. The aroma concentration is slowly increased to reach therequired minimum saturation level required to trigger the pure aromadetection threshold. That digital value becomes a data point for thenostril being tested. A test event result might be based upon an averageof, e.g., 0.000340 ppm on the left side and 0.000580 ppm on the rightside. The ppm score can be converted to a L/R ratio such as,0.000340/0.000580 or some other mathematical notation suitable forstatistical analysis and reporting the data in a useful form to a healthcare provider.

Certain laboratory testing equipment is able to accurately identify andquantify a very specific aroma or exact sets of specific aromas in realtime and displayed concentrations digitally in parts per million. Theseelectronic smelling devices are well known to the skilled artisan.Electronic nose modules are thus very sensitive, but only detect a verynarrow range of organic or chemical odor that they are “fingerprinted”to detect.

Using electronic nose modules in a bilateral clinical aroma detectionthreshold testing device is disclosed. As the concentration of a purearoma in a breathable gas is slowly increased, a real-time digitalreadout slowly rises numerically, until the subject notes in cognitiverecognition that an aroma is detected. The numerical readout may beautomatically fixed or frozen at the level required for cognitive noticethat an aroma has been detected when the test administrator removestheir finger from the aroma control button.

The clinical testing personnel notes the ppm displayed which wasrequired to elicit the reaction and also notes which nostril was beingtested by that particular testing event. Data record keeping may beaccomplished, as described herein, by a computer attached by USB or wireor radio system such as Bluetooth or Wi-Fi, to the testing device ortesting results may be scored and calculated on paper.

Taking a clinically accepted baseline of individual nasal air flowperformance into account, reduces test error and enhances the overallefficacy of the disclosed aroma test. If a person has a severely reducedairflow in one nostril, without taking that issue into account, testresults might be skewed. Below are at least some of the ways to validatea clinically suitable “baseline of nasal performance”.

Relative airflow measurement of the nostrils overcomes most inhalationair volume impediment variables or at least make the testing personnelvisually and/or graphically aware of the issue in a quantitative way.Direct airflow testing with dual gas flown meters, visually comparingthe actual inhalation volume of the two nostrils at the same time, iscertainly the most important consideration for establishing a nasalperformance baseline. A bilateral inhalation airflow testing device aspreviously disclosed has two airflow readout elements displayed side byside to visually compare the nasal inhalation performance of the twonostrils, wherein the testing and comparing is accomplished at the sametime for the two nostrils.

The subject may be shown the readout in a mirror and is asked to inhalegently such that the top ball is near a mark on the readout. The ballthat is constantly lower indicates that the indicated nostril has alower airflow volume. A bleed valve might be provided to “set” the upperlimits and calibrate the readout at the factory. An airflow inhalationtesting device is built into some embodiments of the testing apparatus.Flow meters with a sufficient gas flow rate encompassing maximum nostrilperformance may also be used.

In addition to actually testing the relative airflow of the nostrils,the following items need to be considered in establishing a clinicallyacceptable baseline of nasal performance and the appropriateness oftesting a particular patient with the disclosed devices, systems andmethods.

A medical history of the patient may be obtained in regard to injury tothe nose, the individual nostrils and associated airways and inhalationperformance thereof, known or observed structural abnormalities,significant nose bleeds, a history of sinus infections, known strokes orT.I.A.s, current nasal congestion, a diagnosis of deviated septum, anyprevious nasal surgery, nasal tumors, polyups, allergies, a history ofexposure to strong industrial odors, age, etc., to enhance the clinicalsignificance of the results of the present invention and, potentially,to disqualify certain individuals from taking the test.

An illuminated optical examination of the nasal passage may be executedto identify mucous plugs, serious inflammation or other structural ormedical impediments to a freely flowing nasal airway.

Administering a decongestant or other medicine to open airways may alsobe indicated in certain patient prior to nasal airflow measurements andaroma testing.

Retesting the subject at a later time of the same day or at later datemay also mitigate temporary nasal conditions that might otherwise skewthe test results.

A sliding scale, or corrective factor as described above, tomathematically adjust, or “handicap” the bilateral smelling acuityscores for a non-symmetrical baseline of nasal air flow may be appliedto the aroma scale test results.

Cutoff levels will be established which will disqualify certain peoplefrom being considered a good candidate for the disclosed pure aromadetection test.

The disclosed aroma testing devices may be “tuned” in a number of waysduring the industrial design process towards creating ideal efficacy aswill be understood by the skilled artisan. For example, the diameter ofthe air intake ports, the diameter of gas supply tubes, the diameter ofports into and out of the aroma chamber, the size and diameter of theclear air chamber, the diameter of cannula tubes and disposable nasalcannula parts can be enlarged or constricted to achieve effectivecontrol of aroma concentration. Thus, time intervals or breaths may beadjusted as required to reach a threshold condition through scaling theapparatus. Electronic ultrasonic aroma emitters may also be adjusted tocreate a weaker or stronger aroma concentration.

The concentration of aroma may also be controlled by using various purearoma producing materials and by controlling aroma dilution and theamount used. The surface area of the aroma chamber and surface area ofthe aroma source exposed to passing air are also controllable designvariables. A minimum amount of aroma detectable is preferred, to reducepossible latency of aroma in what is intended to be substantially clearair. Coatings, filters and aroma absorbing elements may be applied tovarious embodiments to repel and/or absorb aroma molecules, therebyreducing latent aroma in what is intended to be substantially clear air.

Aroma sources as described herein may be in the form of a liquid held inan absorbent porous material such as a wick, stiff blotter slide or acotton ball that is placed in the aroma chamber of the test apparatus. Aviscous material such as peanut butter could be wiped onto a slide likeelement and inserted into the aroma chamber or the material supplied ina disposable portion package with removable seal top. Odorants, or pureodorants, may be used as discussed herein.

Such aroma/odorant diffusion devices are suitable to use as a cartridgethat is inserted into the housing of the various devices as describedherein. Such devices are refillable and may be filled with any essentialoil. USB type ultrasonic devices emit little aroma when switched off.They may be used in the test devices of the present inventioncomprising, e.g., a single air chamber, thus reducing the complexity andparts required to manufacture such devices.

Repeating the testing protocol discussed herein a number of times, nomatter which embodiment is used, with a randomized rotation between thenostrils and fully purging unscented airways between testing events,will create a meaningful and repeatably accurate and clinicallyacceptable test result.

As discussed above, the results from the use of the various embodimentsof the devices, systems and methods of the present invention may be usedto identify an asymmetry in a patient's olfactory threshold determinedfor the left and right airways. In the case of pure odorants used in thetesting protocol, e.g., if an olfactory deficiency is detected via ahigher olfactory threshold in the patient's left nostril and associatedairway, this may provide early indication of Alzheimer's disease.

Alternatively, the results from the use of the various embodiments ofthe devices, systems and methods of the present invention may be used toidentify an olfactory dysfunction, as compared with a baseline value,that is generally symmetrical as determined by the patient's olfactorythreshold in the left and right airways. Once this type of dysfunctionis determined, the patient's olfactory threshold may be monitored forseveral purposes including, but not limited to, monitoring the progressof the disease and/or condition contributing at least in part to thesymmetrical olfactory dysfunction and/or monitoring the efficacy of atreatment regimen developed to treat the underlying disease, conditionand/or olfactory dysfunction.

Actually diagnosing AD certainly rests with Doctors. Presenting theresults of a comprehensive medical history analysis and also factoringin any specific AD screening results available, with appropriated weightbeing given each element of medical information, might be produceduniformly by a computerized data base system. The server would run analgorithm designed to weigh relevant data according to theirefficaciousness and specificity for AD and render an AD stage assessmentfor local Doctors.

The disclosed algorithm concept comprises a complex database softwareprogram, factors all known risk factors and screening results, would beutilized to issue an AD risk factor. A universal risk factor scoringmethod would thus assist Doctors in making a clinical diagnosis moreeasily and much earlier in the progression of the disease. The algorithmwould be continually adjusted to increase accuracy as more relevant databecomes available.

It is important for the purposes of doing clinical drug trials thatgroups of patients with early AD and those persons with little AD riskbe identified. A large data base that contains medical histories and ADscreening test results of many patients would allow computer data basedobservational studies to be done.

Designing and running a computerized database report, predicated uponcertain aspects of the data, suspected AD risk factors could be quicklyconfirmed or found to be statistically irrelevant. Assume the data basehas a yes or no answer to the question, “do you snore?” A researcherwants to know if breathing difficulties defined by snoring during sleepmight be a risk factor for AD. Run the data and find out, in mereseconds

Medical History and Screening Information items to be considered in acomprehensive AD Risk Factor Scoring System. This system would separatepatient into low, medium, high and very high risk for AD categories.

The items in an AD medical history inventory are subject to change asnew risk factors are suspected and previously identified potential riskfactors are ruled out. Thus, the questions asked in the medical historyform and the weight given each element are a dynamic that must becontinuously adjusted as more data becomes available.

All AD screening tests included may be given weight based upon specificefficacy, (the occurrence of false positives and false negatives).

While a patient might have a strong risk factor based upon their medicalhistory, an 80 year old with no amyloid plaque deposits on their retinaand no deterioration of the olfactory nerve have virtually no risk ofdeveloping AD before they are statistically dead due to the period ittakes for AD to fully develop.

Re-screening is still recommended however, in case AD indications ariselater on. Also, such a person by eliminating AD, but who has still hassome dementia is helped. Their condition must be due to some othermedical reason and the Doctor needs to know that.

Ruling out AD is just as important as diagnosing it. The relief it wouldgive people to know that they are at a very low risk for ever developingAD means a lapse in memory wouldn't cause panic, fearing that theirminds are slipping away. People who have seen family members deteriorateare certainly emotionally charged regarding that risk in their own case.

A standardized AD Risk Factor System which takes all efficaciousscreening tests and medical history items into account to render a riskscore would tend to create a more universal medical characterization ofAD patient condition, furthering the medical art. A doctor who knows acertain patient has a high risk factor might order a Cur Cumin Study torule out AD.

The proposed Risk Factor material below is far from a finished productas each risk factor is based on recent data a subject to constantrevision.

Sample Medical History and AD Risk Factor questions, an example:

1. Age AD Development Risk Doubles every 5 years after 80

80=0, 85=+10 90=+20 95=+25 100=+5

2. Sex, Female 50% greater risk than men

M=0 F=+50

3. Do you smoke? How many packs a day? 59% risk factor

1=+20 2=+30 3=+40

4. Blood Pressure numbers for Pulse Pressure, over 60 risk factor

PP60=+25 PP65=+30 PP70=+40

5. Total Cholesterol,

180=+20 190=+30 200=+40 210=+50 220=+60 225=65

6. Weight m Midlife Obesity 60% risk factor

BMI at 40 greater than 100=+50

7. Height, Calculate current BMI

8. Family History of AD,

No=0 Yes=+30

9. Do you Snore?

No=0 Yes=+20

10. Been Diagnosed with Sleep apnea?

No=0 Yes=30 Use a CPAP? Yes−10 No=0

11. Education years, Highest Grade level Achieved

6=+50 7=+40 8=+30 9=+20 10=+10 11=0 12=−10 13=−20 14=−30 14=−50

12. How old was your mother when you were born?

30=0 35=+20 40+=+40

13. Do you have migraine headaches?

No=0 Yes=+40

14. Been exposed to fumigants at work, as professional pest control?

No=0 Yes=+50

15. Have you been exposed to defoliants?

No=0 Yes=+50

16. Ever been hospitalized for head trauma, such as a concussion?

No=0 Yes=+40

17. Are you diabetic? Type I or Type II? 46%

No=0 Yes=+50

18. Ever had a stroke?

No=0 Yes=+50

19. Have you been diagnosed with heart disease?

No=0 Yes=+50

20. Have you suffered from serious depression requiring medication? 65%

No=0 Yes=+50

21. Have you had your DNA decoded? AD Risk Gene noted

No=0 Yes=+100

22. Do you take low dose aspirin every day?

No=+50 Yes=0

23. Do you take Blood thinners?

No=+30 Yes=0

24. Women, do you take Estrogen hormone replacement

No=0 Yes=+50

25. Are you Physically inactivity 82%

No=0 Yes=+40

26. Midlife Hypertension 61%

No=0 Yes=+40

27. Hearing loss documented

No=0 Yes=+20

28. Low Cognitive Test Score

No=0 Yes=+200

A risk factor score of 250+Low Risk Factor

A risk factor score of 500+ is stage 2 Moderate Risk Factor

A risk factor score of 750+ is stage 3, High Risk Factor

A risk factor score of 1000+Very High Risk Factor

Basic AD Staging Perimeters

Stage 0 in Alzheimer's disease are those characterized as having nopositive AD screen results noted. A person who has no positive screensresults, despite multiple and significant risk factors may be AD freefor the rest of their natural life span. For example, a person age 75who has no amyloid plaque visualized on their retina whatsoever and hasequal aroma detection ability between their nostrils is unlikely to everdevelop AD or it will be so minor and so late in life that most suchpeople would die of other causes long before serious dementia takesplace. Re-screening Stage 0 patients at least every 5 years might berecommended, especially when helpful medications are finally approved.

Stage 1 in Alzheimer's Disease is characterized as the incipient stage,where dementia is not noticeable and plaque deposits on the retina arepresent but very limited. The aroma scale screen might show a slightlyloss of aroma detection on the left side, blood tests might show a verylimited amount of AD associated lipids. The lowest level of detectablecharacteristics of AD onset by any set of dependable screening methodsbroadly define Stage 1.

Stage 2 in Alzheimer's disease is characterized as the AD developmentstage when significant plaque is deposited in brain and retinal tissue.The aroma scale would show a marked loss of pure aroma detection on theleft side and a serious cognitive decline will be noticed by the patientand family. Low levels of AD related lipids would be noted in ADscreening blood tests, PET scans would show plaque at detectable levelson the brain.

Stage 3 in Alzheimer's disease is characterized by profound memory lossissues, very notable plaque deposits in brain and retinal tissue,significant loss of pure aroma detection on the left side would be notedand higher levels of AD related lipids would be noted in AD blood tests.

Stage 4 in Alzheimer's disease is characterized by severely impactedmemory issues, very significant plaque deposits on the brains andretinal tissue, A profound loss of pure aroma detection ability in theleft side and a recent decline in aroma detection on the right side, aswell. Stage 4 is the terminal stage of Alzheimer's disease.

Managing Global Testing Data

No medical testing apparatus or method has diagnostic value without aconvincing amount of data to document efficacy. The combination of thedisclosed handheld aroma testing mechanism and aroma testing protocolwith associated data can be well managed to have dramatic potential formany purposes.

From the medical provider's point of view, there is an internet basedweb site containing the most recent information on the aroma scale test,provider account registration and the practice's data for its patientsbehind a secure login infrastructure.

The medical provider establishes an account for their practice thatincludes providing a physical clinic shipping address, phone numbers,credit card account information, a designated email account and othercontact information.

A password protected “provider account” is thus set up to support theonline purchase of Aroma Scale devices, consumable Aroma Cartridges,nostril airflow testing meters, etc. A unique Medical Provider Accountidentifier code is provided which is used in establishing secure patientfile access. Provider accounts include an automatic payment systemutilizing a credit card for paying for aroma scale reporting servicesand products.

A computer application that runs on iPad, iPhone, Android, Macs and PCsallows secure patient data files to be established and the data accessedby the medical provider.

Secure Patient files contain relevant medical history, nostril airflowdata and dated aroma scale test data for any patient given the aromascore screening test. This account information is “HEPPA secure” and mayrequire the use of unique patient identifier codes that only the doctorcan correlate with any particular patient. Follow up aroma testing isadded to the existing patient file along with date and relevant medicalhistory information.

The computer application may be in the form of a stand-alone “App” thatis distributed free, by Apple Computer Company and various Android AppStores. Alternatively, a web based HTML5 App would be available offeringsimilar functions running on common web browsers.

To begin using the Aroma Scale screening system a provider would set upa provider account, order aroma scale testing apparatus and train nurseswho will administer the test in their clinics. Training may be done byusing a DVD or viewing videos posted on line.

A database populated with numerous patient files would allow for“virtual” observational clinical studies. Further medical historyinformation may be added periodically to updated data input forms, ashelpful risk factors are proposed. Requests for database analysisreports would be fulfilled by the central computer database under thecontrol of the Aroma Score Company.

An extensive database would provide candidates for drug studies sinceknown early onset AD and similarly situated people who are not earlyonset AD would be searchable by locality. The demand for highlyconcentrated early onset AD patients who are local and willing toparticipate in clinical trials is a major obstacle for the drugindustry, worldwide in doing clinical trials.

Screening a Patient Includes the Protocol Elements of:

1. Opening a new online data entry form using an application or webform. The data entry form requires every block of data requested beentered before going to the following page to insure complete files.

2. A medical history page includes, the provider account identifiercode, the system automatically loads the date of the test, requires anentry that encrypts a novel patient identifier code, records date ofbirth, sex, weight etc., including relevant known medical history,nostril airflow numbers and the Aroma Scale raw data.

3. Upon completing the patient data entry form the nurse enters “Submit”to send the new patient file over the internet to the Aroma Scorecentral server. This completes the test and data entry portion of theAroma Score management method.

4. Upon receiving the patient data file over an internet connection, thecentral server adds the disclosed information to a central data base andcorrelates the instant data provided with all existing data on theserver.

5. The server then uses a proprietary algorithm to generate an AD riskscore for that particular patient considering all the medical historyand testing data amassed globally.

6. The server then charges the medical provider's credit card aprocessing fee for providing an AD risk score. Follow-up Aroma Scoringprocessing might be free for registered patients to encourageparticipation with the program long term.

7. The server then sends the medical provider an email that include theencrypted patient identification code, the report lists known riskfactors for AD and an Aroma Scale Risk Assessment.

8. The medical provider then uses the Aroma Scale Risk Assessment toassist in making a diagnosis or decision to do more AD risk testing. Thediagnosis could include, planning a follow up aroma scale screen in thefuture, doing alternative testing to confirm or exclude incipient AD incase of a high risk assessment. The risk assessment may completely clearthe patient, for the time being.

Aroma Scale Risk Assessment Reports Might be Similar to these Examples:

RHeilMD@doctorsrock.com

Re; AromaScore Results for patient 6562GS78

Dr. Heil:

Your office submitted AromaScale AD screening history and test data forpatient 6562GS78 on Jun. 5, 2014. Due to the following risk factors, weassign the highest risk factor to this patient. Further diagnostictesting is recommended with a follow up AromaScale screening in 6months.

Patent Code: 6562GS78

Risk Factors for AD

1. Sex, Patient is female, 50% greater chance of developing AD

2. Age, patient is 83, risk doubles for AD every 5 years after age 80

3. Mild Dementia Noted, due to age and limited extent of dementia notedthis may not be relevant, yet

4. Sleep Apnea, Patient reports sleep study indicating sleep apnea,moderate enhanced risk

5. Pulse Pressure High, 165/87, Pulse pressure well over 60 points, HighRisk factor

6. Family History of AD, slight added risk factor due to one parenthaving AD at an age prior to 90

7. AromaScale Screen Results, 47 Left/33 Right, no significant bilateralair flow factor.

VERY HIGH RISK for early onset AD is predicted.

NOTE: Doctor Heil,

Due to the above noted high risk factors, further diagnostic testing isclearly recommended for this patient.

Patient should be advised to prepare for a notable decline in hercognitive condition over the next few years. Preparation might includeobtaining long term health care insurance if she is not already covered.Any care givers need to be advised that her dementia symptoms mayincrease in the short term.

Follow up AromaScale testing is free, please participate in our clinicaltrial by helping us follow this patient's condition. Patient may beasked if they would be interested in being part of a clinical studytesting new AD medicines. Such medicines might help them avoid furtherdementia.

Thank you, the AromaScale Team

Cur Cumin Stained Amyloid Plaque AD Screen/Confirmation

Another early onset AD screening method of great interest to the medicalindustry has been staining amyloid plaque and then visually identifyingthe plaque in the eye of a living person through the iris.

One particularly helpful “smart tag” is the bright yellow Indian spiceCur Cumin. Being hydrophobic, ingested or injected cur cumin moleculesjump the blood brain barrier to attach to a molecularly sticky spot onAmyloid plaque deposits. Since some eye tissue, (notably the retina), isneural tissue much like the brain, deposits of plaque develop thereconcurrently with the brain and fortunately can be visualized withoutinvasive procedures.

While cur cumin stained plaques may be visualized with white light, UVlight at around 400 nm tends to create a fluorescence effect with anorange glow that contrasts nicely with unstained retinal tissue tendingto be another color of yellow. The plaque can be viewed through the iriswith or without dilating the eye. Common Ophthalmology examination toolsfor visualizing the retina may be used. The gold standard of retinalexamination is the dilated view of the retina.

Administering natural Cur Cumin and then examining the eye and notfinding any amyloid plaque amounts to a quite persuasive negative screenresult for incident AD. No plaque, no AD. Alternative causes for plaqueon the retina or other features that might be notable may be discountedthrough prior examination of the eye by a qualified ophthalmologist. Abaseline and cur cumin stained retinal image can tell a trainedOphthalmologist a lot.

Fundus photography is used to document abnormalities of the eye ordisease progression and may be used for conditions such as maculardegeneration, glaucoma, neoplasms of the retina and choroid (benign andmalignant), retinal hemorrhages, ischemia, retinal detachment, choroiddisturbances, and diabetic retinopathy. It may also be used forassessment of recently performed retinal laser surgery.

While research has been done using chemical derivatives of Cur Cumin tosupposedly enhance the effect, shift the wavelength of light thatexcites or is fluoresced by certain wavelengths of light, natural curcumin works well at around 400 nm without chemical enhancement of thespice. Light that simply contains the 400 nm light with otherwavelengths as well still shows the plaque to the trained eye of adoctor of Ophthalmology.

Cur Cumin has been allowed legally in the United States as a foodsupplement and as a spice, used without serious contra-indications formany years. The effect of natural cur cumin seen on retinal tissue iswell known.

What is lacking in using cur cumin as a screening method for findingAmyloid Plaque as a screen for early onset AD is a scoring method thatquantifies the plaque deposits. Digital images of the retina may be sentvia the internet and stored on servers for later examination by aqualified Doctor of Ophthalmology. A set of retinal images taken overtime show a progression of the AD disease process as additional plaqueis deposited.

Data show that while cur cumin taken orally stains amyloid plaquedeposits on the retina, those patients without plaque deposits show nodifference between a baseline retinal photograph and a series ofphotographs taken daily with a 800 mg dose of the staining agent curcumin.

Some research indicates that cur cumin in the blood stream reaches amaximum in an hour after ingestion if it has an oil additive or a pepperextract added to aid in absorption by the body. The cur cumin in theblood steam jumps to the plaque and adheres to it creating the visualeffect needed to identify retinal plaques.

Cur Cumin Stained Retinal Amyloid Plaque Detection and Scoring MethodAmyloid plaque in the eye has been detected when such plaque is stainedby an appropriate agent. The staining agent is applied topically to theexterior of the eye with some screens and are taken orally or injectedinto the blood screen to stain any plaque on the eye. Plaque may thus beseen both on the cornea and the retina. Of the methods above used toadminister cur cumin, ingestion is the least troublesome to the patientand provides sufficient effect on retinal plaque to work well as ascreening system.

Recently, methods of visualizing and identifying amyloid plaque inliving patients have been demonstrated. Various cur cumin deviates andalternative stains such as Congo Red, special optical detection devicesand methods of detection have been proposed.

However, a meaningful scoring method has yet to be introduced to themedical community to quantify such deposits seen in the eye. Evidencethat cur cumin stained retinal plaque has in fact been detected in apatient's eye really doesn't facilitate a meaningful diagnosis,particularly as to staging without a universal method of comparison.

A retinal plaque stained screen method using orally administerednaturally occurring cur cumin is particularly efficacious with certainsteps taken to prevent false positives due to alternative reasons suchplaque might be present.

Cur Cumin Retinal Study Protocol

A patient suspected of having early onset AD due to an aroma screen isreferred by their general practitioner or neurologist to a localophthalmologist. The local ophthalmologist observes the eye grounds andtakes a detailed digital picture of the retina. The patient is thengiven cur cumin in tablet form to ingest and given a second appointment.

The follow-up appointment is to have their eye(s) re-examined after aperiod required for their body to absorb the cur cumin and have the curcumin jump the blood brain barrier to attach to a receptive area on anyretinal plaque that might be present in the eye.

At the second local Ophthalmologist appointment, the eyes are examinedagain and a second retinal digital photograph is taken using light andor filters including wave lengths around 400 nm (+ or −20 nm) At thosewave length, natural cur cumin which has bonded to any retinal plaquehas a fluorescence in a bright orange color that contrasts withunstained retinal tissue. The plaque is thus easily noticeable ifpresent. A lack of plaque deposits is also visually apparent in detaileddigital retinal digital photographs

While strong UV light around 265 nm is harmful to eye tissue, light inthe range that fluoresces cur cumin is not dangerous, especially atfairly low levels and for short periods of time.

The local ophthalmologist does not confirm or deny that plaque wasvisualized and then emails the first and second retinal photographs to acentral server where a board certified ophthalmologist remotely readsthe digital pictures to stage the plaque based upon a zero for no plaqueto a higher scale number based upon the relative amount of plaque seen.

No plaque whatsoever seen means that AD is not in early stages andamounts to a negative screening result. Clearly, amyloid plaque, whendetected is significant. Having also seen a baseline retinal photographof the eye's condition before the cur cumin stain and considering themedical history of the patient allows the doctor to rule out alternativereasons such plaque is seen that are due to alternative conditions thanAD.

The diagnosis of retinal plaque and its relative concentration isreported back to the local general practitioner or neurologist who mayinform the patient, order other confirming screens or advise the patientthat there is no indication of AD development at this time.

Staging AD from the retinal image is:

Stage 0, a negative result of the study, the patient is not developingAD.

Stage 1, the minimum amount of plaque detectable, this person is likelyearly onset for AD.

Stage 2, Plaque is clearly notable and in greater amounts than stage 1.

Stage 3, The plaque is very notable and in greater concentration thanstage 3

Stage 4, the most plaque seen in such studies, this person is profoundlydiseased and likely in the terminal stage 4 of AD.

The local Doctor is then advised by email sent only to a designatedemail address for their practice by the central screening system, as tothe relative amount of retinal plaque seen and a comprehensive AD riskscore.

The cur cumin testing protocol may be used as an additional AD screeningtool following a positive screen using the above methods, devices andsystems. Alternatively, the cur cumin testing protocol may be used as aconfirmatory AD test, following a positive screen using the abovemethods, devices and systems.

The present invention should not be considered limited to the particularexamples described above, but rather should be understood to cover allaspects of the invention. Various modifications, equivalent processes,as well as numerous structures to which the present invention may beapplicable will be readily apparent to those of skill in the art towhich the present invention is directed upon review of the presentspecification.

1. A method for screening a patient for Alzheimer's disease, the patienthaving a first nostril and a second nostril, the method comprising:providing at least two pure odorants; establishing an introduction orderfor the at least two pure odorants; introducing pure odorant-infused airin the established introduction order to the patient's first nostril,wherein the first nostril is either the right or left nostril, without areset period between successively introduced pure odorant-infused air;measuring and recording a pure odorant detection metric for each of thepure odorant-infused air introductions; introducing pure odorant-infusedair in the established introduction order to the patient's secondnostril without a reset period between successively introduced pureodorant-infused air; measuring and recording a pure odorant detectionmetric for each of the pure odorant-infused air introductions; comparingthe recorded pure odorant detection metric for the first nostril and thesecond nostril to obtain a relative pure odorant detection thresholdvalue for each nostril; determining whether the obtained relative pureodorant detection threshold value for the first nostril statisticallydiffers from the obtained relative pure odorant detection threshold forthe second nostril; and concluding that, if the patient's pure odorantdetection threshold value for the patient's left nostril isstatistically greater than pure odorant detection threshold value forthe patient's right nostril, the patient's olfactory organ may besignificantly impacted by Alzheimer's disease.
 2. The method of claim 1,wherein the recorded metric comprises the total time and/or the totalnumber of breaths required by the patient to reach the pure odorantdetection threshold.
 3. The method of claim 1, wherein the pure odorantdetection threshold consists of the point at which the concentration ofpure odorant molecules for each one of the pure odorants introducedsaturate the patient's olfactory nerve to the extent that a cognitivereaction occurs in the patient.
 4. The method of claim 1, furthercomprising each pure odorant consisting of a substance that stimulatesthe olfactory cell receptors of the first cranial nerve and that do notstimulate the fifth cranial nerve.
 5. The method of claim 1, furthercomprising: immediately switching from presenting a first pure odorantair flow to one of the patient's nostrils upon cognitive notice of thefirst pure odorant by the patient indicating reaching of the puredetection threshold for the first pure odorant with the nostril; andpresenting a second pure odorant air flow to the nostril, whereupon thepatient's cognitive notice of the first pure odorant is replaced bycognitive notice of the second pure odorant when the pure odorantdetection threshold is reached for the second pure odorant, without aidof a reset period interposed between the presenting of the first pureodorant air flow and the presenting of the second pure odorant air flow.6. The method of claim 1, wherein the pure odorant detection metricfurther comprises the sum of periods measured in seconds elapsed betweenthe presentation of the first pure odorant of the at least two pureodorants and the patient's cognitive notice of the first pure odorant,followed by immediate switching to the second pure odorant of the atleast two pure odorants and presentation of the second pure odorant ofthe at least two pure odorants, and the patient's cognitive notice ofthe second pure odorant of the at least two pure odorants.
 7. The methodof claim 6, further comprising comparing the summed pure odorant metricsfor the left nostril and the right nostril and determining whether theleft nostril's summed pure odorant metric statistically differs from thesummed pure odorant metric for the right nostril.
 8. The method of claim7, further comprising concluding that the patient's olfactory organ maybe significantly impacted by Alzheimer's disease if the summed pureodorant metrics for the left nostril are statistically greater than thesummed pure odorant metrics for the right nostril.
 9. The method ofclaim 1, further comprising the at least two pure odorants consisting ofthe same pure odorant wherein the established introduction ordercomprises the pure odorant in successively increasing concentrationuntil cognitive notice indicating the patient has reached the pureodorant detection threshold.
 10. The method of claim 1, furthercomprising providing a device to introduce the at least two pureodorants in pure odorant infused-air to each of the patient's nostrils.11. The method of claim 10, the device further comprising oleophobicairways.
 12. The method of claim 10, the device comprising: a hand-heldhousing defining a chamber therein in valved communication with externalatmospheric air; a nasal tip with a lumen therethrough, the lumen influid communication with the housing chamber; a pure odorant cartridgecomprising a substantially circular rigid body and having two sides,further comprising more than two pure odorant chambers defined by therigid body, the more than two pure odorant chambers arrangedsequentially, and the cartridge being rotatably disposed in the housing;and a pure odorant disposed within each of the more than twosequentially arranged pure odorant chambers, wherein the sequentiallyarranged pure odorant chambers are successively rotatably aligned toenable a selected pure odorant chamber to move into fluid communicationwith the housing chamber and the nasal tip lumen.
 13. The method ofclaim 12, wherein the more than two pure odorants comprise a single pureodorant with successively increasing concentrations disposed insuccessive and adjacent pure odorant chambers until cognitive noticeindicating the patient has reached the pure odorant detection threshold.14. The method of claim 12, the pure odorant cartridge comprising: asubstantially circular rigid central body and having two sides; and morethan two pure odorant chambers defined by the rigid body, each chamberarranged to hold an effective amount of one pure odorant, the more thantwo pure odorant chambers arranged sequentially.
 15. The method of claim14, wherein the pure odorant cartridge further comprises a slotalignable with the position of each of the two or more pure odorantchambers in succession, the slot allowing atmospheric air to passthrough the aligned pure odorant chamber to create the pureodorant-infused air for presentation to the nasal tip.
 16. The method ofclaim 15, further comprising: immediately advancing the pure odorantcartridge from the presenting of pure odorant infused air of a firstpure odorant disposed in a first pure odorant chamber of the pureodorant cartridge to the patient's nostril upon the patient's cognitivenotice of the first pure odorant, indicating the patient has reached thepure odorant detection threshold for the nostril and the first pureodorant; and presenting a second pure odorant infused air of a secondpure odorant disposed in a second pure odorant chamber adjacent thefirst pure odorant chamber of the pure odorant cartridge to thepatient's nostril, and without aid of a reset period interposed betweenpresentation of the first pure odorant infused air and the presentationof the second pure odorant infused air to the patient's nostril untilthe patient's cognitive notice of the second pure odorant indicating thepatient has reached the pure odorant detection threshold for the nostriland the second pure odorant.
 17. The method of claim 14, wherein atleast one chamber of the pure odorant cartridge contains no pure odorantand is, therefore blank.
 18. The method of claim 17, further comprisingruling out pure odorant contamination of the device if the patientcannot smell a pure odorant when the blank chamber of the pure odorantcartridge is aligned with the patient's nostril.
 19. The method of claim10, the device further comprising a bilateral visual indication thatsufficient airflow is present to ensure valid results.